Purpose

This phase II MATCH trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)

- Women of childbearing potential must have a negative serum pregnancy test within 2
weeks prior to registration; patients that are pregnant or breast feeding are
excluded; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 4 months after completion of study;
should a woman become pregnant or suspect while she or her partner is participating in
this study, she should inform her treating physician immediately

- Patients must have histologically documented solid tumors or histologically confirmed
diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the
following criteria:

- Patients must have progressed following at least one line of standard systemic
therapy and there must not be other approval/standard therapy available that has
been shown to prolong overall survival (i.e. in a randomized trial against
another standard treatment or by comparison to historical controls); patients who
cannot receive other standard therapy that has been shown to prolong overall
survival due to medical issues will be eligible, if other eligibility criteria
are met; if the patient is currently receiving therapy, the clinician must have
assessed that the current therapy is no longer benefitting the patient prior to
enrolling on MATCH, regardless of whether it is considered standard OR

- Patients for whose disease no standard treatment exists that has been shown to
prolong overall survival

- NOTE: No other prior malignancy is allowed except for the following:

- Adequately treated basal cell or squamous cell skin cancer

- In situ cervical cancer

- Adequately treated stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which the patient has been disease-free for 5 years

- Patients must have measurable disease

- Patients must meet the criteria below and have received results from one of the
designated outside laboratories indicating a "rare variant" that is an actionable
Mutation of Interest (aMOI) for specific select subprotocols.

- The following requirements apply:

- The outside laboratory specifically notified the site that patient may be a
potential candidate for MATCH due to a detected "rare variant"; the outside
lab reports are NOT sufficient for this purpose

- NOTE: The content and format of these specific notifications for the
Outside Assay process will vary depending on the designated outside lab
in question, as they are each responsible for their own outreach
efforts; it is strongly recommended that the designated outside
laboratory be contacted to confirm the format and receipt of this
notification prior to registering any patients to Step 0

- Patients with an applicable "rare variant" must be able to meet the
eligibility criteria for the appropriate subprotocols within 4 weeks
following notification of treatment assignment

- NOTE: The receipt of this notification (and the start of the associated
deadline for Step 1 registration) may occur shortly after Step 0
registration, since these patients will not be submitting tissue for
screening purposes; however, for certain "rare variant" arms,
submission of archival tissue for central immunohistochemistry (IHC)
testing may be required

- Registration to Step 0 must occur after stopping prior systemic anti-cancer
therapy; there is no specific duration for which patients must be off
treatment prior to registration to Step 0, as long as all eligibility
criteria are met

- There is no particular window of time after notification of potential
eligibility from an outside lab in which the patient must be registered to
Step 0, but treatment slots will be assigned on a first come, first serve
basis to those who do register to Step 0, and are not held for those
notified of potential eligibility who do not register to Step 0

- Patients may have received other non-targeted, immunotherapy or targeted
treatment between the prior genetic testing at the outside lab and
registration to Step 0; the decision to stop such treatment in favor of
participation in MATCH, if no further clinical benefit is expected, is per
the treating physician's discretion; documentation of a lack of response to
the prior treatment is not required in these cases

- NOTE: Other potential aMOIs that would be eligibility criteria for "NON
RARE" arms, as determined by the designated laboratories, are not
applicable for this process in MATCH

- NOTE: Tumor tissue for the confirmation of "rare variant" by the MATCH
assay is to be submitted, preferably from the same time of collection
as that evaluated by the designated outside laboratory

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
and a life expectancy of at least 3 months

- Patients must be able to swallow tablets or capsules; a patient with any
gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
is not eligible

- Patients who are human immunodeficiency virus (HIV)-positive are eligible if:

- CD4+ cell count greater or equal to 250 cells/mm^3

- If patient is on antiretroviral therapy, there must be minimal interactions or
overlapping toxicity of the antiretroviral therapy with the experimental cancer
treatment; for experimental cancer therapeutics with CYP3A/4 interactions,
protease inhibitor therapy is disallowed; suggested regimens to replace protease
inhibitor therapy include dolutegravir given with tenofovir/emtricitabine;
raltegravir given with tenofovir and emtricitabine; once daily combinations that
use pharmacologic boosters may not be used

- No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining
conditions other than historical low CD4+ cell counts

- Probable long-term survival with HIV if cancer were not present

- Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy]
or less), or major surgery must have been completed >= 4 weeks prior to start of
treatment; all adverse events due to prior therapy have resolved to a grade 1 or
better (except alopecia and lymphopenia) by start of treatment; palliative radiation
therapy must have been completed at least 2 weeks prior to start of treatment; the
radiotherapy must not be to a lesion that is included as measurable disease

- NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing
hormone (LHRH) agonist

- NOTE: For patients entering the study via the original screening process,
patients may receive non-protocol treatment after biopsy (if clinically
indicated) until they receive notification of results; however, lack of response
must be documented prior to registration to Step 1; new non-protocol treatment
will NOT be permitted as intervening therapy after registration to Step 0; the
only intervening treatment permitted is prior therapy that the patient already
received prior to Step 0 registration; the decision to stop the intervening
non-protocol treatment will be left up to the treating physician if patient has
an aMOI; however, patients will need to be off such therapy for at least 4 weeks
before receiving any MATCH protocol treatment

- NOTE: For patients entering the study via a designated outside laboratory, no
intervening systemic non-protocol treatment is permitted after Step 0
registration; all other eligibility requirements still apply to these patients,
including the washouts for prior therapy noted above in this section, the time
restrictions outlined, and the eligibility criteria for the intended subprotocol

- Patients with brain metastases or primary brain tumors must have completed treatment,
surgery or radiation therapy >= 4 weeks prior to start of treatment

- Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and
remain off steroids thereafter, except as permitted; patients with glioblastoma (GBM)
must have been on stable dose of steroids, or be off steroids, for one week prior to
registration to treatment (Step 1, 3, 5, 7)

- NOTE: The following steroids are permitted (low dose steroid use is defined as
prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):

- Temporary steroid use: e.g. for computed tomography (CT) imaging in setting
of contrast allergy

- Low dose steroid use for appetite

- Chronic inhaled steroid use

- Steroid injections for joint disease

- Stable dose of replacement steroid for adrenal insufficiency or low doses
for non-malignant disease

- Topical steroid

- Steroids required to manage toxicity related to study treatment, as
described in the subprotocols

- Steroids required as pre- or post-chemotherapy medication for acceptable
intervening chemotherapy

- NOTE: Steroids must be completed alongside last dose of chemotherapy

- Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)

- Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to screening step
registration and within 4 weeks prior to treatment step registration)

- Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)

- NOTE: Patients with documented bone marrow involvement by lymphoma are not required to
meet the above hematologic parameters, but must have a platelet count of at least
75,000/mcL and neutrophil count of at least 1,000/mcL

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented
Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)

- Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal

- As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening
step registration and within 4 weeks prior to treatment step registration)

- Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to
screening step and must meet the following cardiac criteria:

- Resting corrected QT interval (QTc) =< 480 msec

- NOTE: If the first recorded QTc exceeds 480 msec, two additional,
consecutive ECGs are required and must result in a mean resting QTc =< 480
msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks
between the ECGs

- The following only need to be assessed if the mean QTc > 480 msec

- Check potassium and magnesium serum levels

- Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG
to confirm exclusion of patient due to QTc

- For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual
read of QTc is required

- For patients with baseline HR < 60 or > 100 bpm, manual read of QT by
trained personnel is required, with Fridericia correction applied to
determine QTc

- Patient must not have hypokalemia (value < institutional lower limit of
normal)

- No factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, congenital long QT syndrome, family history of long
QT syndrome or unexplained sudden death under 40 years of age or any concomitant
medication known to prolong the QT interval

- NOTE: Patient must be taken off prohibited medication prior to registration
to the screening step (Step 0, 2, 4, 6) and remain off these medications
thereafter, unless permitted on a subprotocol for the management of
treatment related toxicity; patient must be off the drug for at least 5
half-lives prior to registration to the treatment step (Step 1, 3, 5, 7);
the medication half-life can be found in the package insert for Food and
Drug Administration (FDA) approved drugs

- ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)

- If patients have been biopsied or submitted archived tumor tissue obtained within the
last 6 months for assessment with the MATCH assays, patients may receive non-protocol
treatment after biopsy/tissue submission (if clinically indicated) until they receive
notification of results however, lack of response must be documented prior to
registration to step 1; new non-protocol treatment will NOT be permitted as
intervening therapy after registration to Step 0; for patients entering step 0 with
assay results from outside laboratories, no systemic treatment is allowed after step 0
registration; the decision to stop the intervening nonprotocol treatment will be left
up to the treating physician if patient has an aMOI; waiting periods as described will
apply

- As MATCH is designed to add additional subprotocols, implement limited expansions of
accrual for certain subprotocols, and/or amend existing arm-specific eligibility
criteria, some patients entering under the original screening method may be eligible
to have their results rerun in MATCHbox, even if they did not match to a treatment
initially or did not receive a treatment assignment due to a lack of available
assignment slots; patients whose sequence results will be rerun through MATCHbox must
also meet the following criteria:

- Samples must have been collected within 5 months of the activation of the
addendum, as there is an additional month needed to get the patients on trial

- Patient has not had treatment within the 5 months that resulted in a PR or better
after the performance of the screening assessment

- Patient must meet eligibility criteria, including performance status 1 or better
and life expectancy of at least 3 months

- Patients must meet the eligibility requirements with the following exceptions:

- Patients may have received other non-targeted, immunotherapy or targeted
treatment, which could be stopped in favor of returning to MATCH, if no
response to the interim treatment has occurred and no further benefit is
expected from this interim treatment, per the treating physician's
discretion; documentation o

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Subprotocol A (EGFR activating mutation)
Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Afatinib
    Given PO
    Other names:
    • BIBW 2992
    • BIBW2992
  • Drug: Afatinib Dimaleate
    Given PO
    Other names:
    • (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
    • BIBW 2992MA2
    • BIBW2992 MA2
    • Gilotrif
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol B (HER2 activating mutation)
Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Afatinib
    Given PO
    Other names:
    • BIBW 2992
    • BIBW2992
  • Drug: Afatinib Dimaleate
    Given PO
    Other names:
    • (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
    • BIBW 2992MA2
    • BIBW2992 MA2
    • Gilotrif
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol C1 (MET amplification)
Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Crizotinib
    Given PO
    Other names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol C2 (MET exon 14 deletion/mutation)
Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Crizotinib
    Given PO
    Other names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol E (EGFR T790M or rare activating mutation)
Patients with EGFR T790M or rare activating mutation receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Osimertinib
    Given PO
    Other names:
    • AZD-9291
    • AZD9291
    • Mereletinib
    • Tagrisso
Experimental
Subprotocol F (ALK translocation)
Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Crizotinib
    Given PO
    Other names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol G (ROS1 translocation or inversion)
Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Crizotinib
    Given PO
    Other names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol H (BRAF V600E/R/K/D mutation)
Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Dabrafenib
    Given PO
    Other names:
    • BRAF Inhibitor GSK2118436
    • GSK-2118436
    • GSK-2118436A
    • GSK2118436
  • Drug: Dabrafenib Mesylate
    Given PO
    Other names:
    • Dabrafenib Methanesulfonate
    • GSK2118436 Methane Sulfonate Salt
    • GSK2118436B
    • Tafinlar
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Trametinib
    Given PO
    Other names:
    • GSK1120212
    • JTP-74057
    • MEK Inhibitor GSK1120212
    • Mekinist
Experimental
Subprotocol I (PIK3CA mutation)
Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Taselisib
    Given PO
    Other names:
    • GDC-0032
    • RO5537381
Experimental
Subprotocol J (HER2 amplification >= 7 copy numbers)
Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Biological: Pertuzumab
    Given IV
    Other names:
    • 2C4
    • 2C4 Antibody
    • MoAb 2C4
    • Monoclonal Antibody 2C4
    • Omnitarg
    • Perjeta
    • rhuMAb2C4
    • RO4368451
  • Biological: Trastuzumab
    Given IV
    Other names:
    • ABP 980
    • ALT02
    • Anti-c-ERB-2
    • Anti-c-erbB2 Monoclonal Antibody
    • Anti-ERB-2
    • Anti-erbB-2
    • Anti-erbB2 Monoclonal Antibody
    • Anti-HER2/c-erbB2 Monoclonal Antibody
    • Anti-p185-HER2
    • c-erb-2 Monoclonal Antibody
    • HER2 Monoclonal Antibody
    • Herceptin
    • Herceptin Biosimilar PF-05280014
    • Herceptin Trastuzumab Biosimilar PF-05280014
    • Herzuma
    • Kanjinti
    • MoAb HER2
    • Monoclonal Antibody c-erb-2
    • Monoclonal Antibody HER2
    • Ogivri
    • Ontruzant
    • PF-05280014
    • rhuMAb HER2
    • RO0452317
    • SB3
    • Trastuzumab Biosimilar ABP 980
    • Trastuzumab Biosimilar ALT02
    • trastuzumab biosimilar EG12014
    • Trastuzumab Biosimilar GB221
    • Trastuzumab Biosimilar HLX02
    • Trastuzumab Biosimilar PF-05280014
    • Trastuzumab Biosimilar SB3
    • Trastuzumab-anns
    • Trastuzumab-dkst
    • Trastuzumab-dttb
    • Trastuzumab-pkrb
    • Trastuzumab-qyyp
    • Trazimera
  • Biological: Trastuzumab Emtansine
    Given IV
    Other names:
    • Ado Trastuzumab Emtansine
    • ADO-Trastuzumab Emtansine
    • Kadcyla
    • PRO132365
    • RO5304020
    • T-DM1
    • Trastuzumab-DM1
    • Trastuzumab-MCC-DM1
    • Trastuzumab-MCC-DM1 Antibody-Drug Conjugate
    • Trastuzumab-MCC-DM1 Immunoconjugate
Experimental
Subprotocol K1 (FGFR amplification)
Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Erdafitinib
    Given PO
    Other names:
    • Balversa
    • JNJ-42756493
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol K2 (FGFR mutation or fusion)
Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Erdafitinib
    Given PO
    Other names:
    • Balversa
    • JNJ-42756493
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol L (mTOR mutation)
Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Sapanisertib
    Given PO
    Other names:
    • INK-128
    • INK128
    • MLN-0128
    • MLN0128
    • TAK-228
Experimental
Subprotocol M (TSC1 or TSC2 mutation)
Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Sapanisertib
    Given PO
    Other names:
    • INK-128
    • INK128
    • MLN-0128
    • MLN0128
    • TAK-228
Experimental
Subprotocol N (PTEN mutation or deletion and PTEN expression)
Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: PI3K-beta Inhibitor GSK2636771
    Given PO
    Other names:
    • GSK2636771
Experimental
Subprotocol P (PTEN loss)
Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: PI3K-beta Inhibitor GSK2636771
    Given PO
    Other names:
    • GSK2636771
Experimental
Subprotocol Q (HER2 amplification)
Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Biological: Trastuzumab
    Given IV
    Other names:
    • ABP 980
    • ALT02
    • Anti-c-ERB-2
    • Anti-c-erbB2 Monoclonal Antibody
    • Anti-ERB-2
    • Anti-erbB-2
    • Anti-erbB2 Monoclonal Antibody
    • Anti-HER2/c-erbB2 Monoclonal Antibody
    • Anti-p185-HER2
    • c-erb-2 Monoclonal Antibody
    • HER2 Monoclonal Antibody
    • Herceptin
    • Herceptin Biosimilar PF-05280014
    • Herceptin Trastuzumab Biosimilar PF-05280014
    • Herzuma
    • Kanjinti
    • MoAb HER2
    • Monoclonal Antibody c-erb-2
    • Monoclonal Antibody HER2
    • Ogivri
    • Ontruzant
    • PF-05280014
    • rhuMAb HER2
    • RO0452317
    • SB3
    • Trastuzumab Biosimilar ABP 980
    • Trastuzumab Biosimilar ALT02
    • trastuzumab biosimilar EG12014
    • Trastuzumab Biosimilar GB221
    • Trastuzumab Biosimilar HLX02
    • Trastuzumab Biosimilar PF-05280014
    • Trastuzumab Biosimilar SB3
    • Trastuzumab-anns
    • Trastuzumab-dkst
    • Trastuzumab-dttb
    • Trastuzumab-pkrb
    • Trastuzumab-qyyp
    • Trazimera
  • Biological: Trastuzumab Emtansine
    Given IV
    Other names:
    • Ado Trastuzumab Emtansine
    • ADO-Trastuzumab Emtansine
    • Kadcyla
    • PRO132365
    • RO5304020
    • T-DM1
    • Trastuzumab-DM1
    • Trastuzumab-MCC-DM1
    • Trastuzumab-MCC-DM1 Antibody-Drug Conjugate
    • Trastuzumab-MCC-DM1 Immunoconjugate
Experimental
Subprotocol R (BRAF fusion or BRAF non-V600 mutation)
Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Trametinib
    Given PO
    Other names:
    • GSK1120212
    • JTP-74057
    • MEK Inhibitor GSK1120212
    • Mekinist
Experimental
Subprotocol S1 (NF1 mutation)
Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Trametinib
    Given PO
    Other names:
    • GSK1120212
    • JTP-74057
    • MEK Inhibitor GSK1120212
    • Mekinist
Experimental
Subprotocol S2 (GNAQ or GNA11 mutation)
Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Trametinib
    Given PO
    Other names:
    • GSK1120212
    • JTP-74057
    • MEK Inhibitor GSK1120212
    • Mekinist
Experimental
Subprotocol T (SMO or PTCH1 mutation)
Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Vismodegib
    Given PO
    Other names:
    • Erivedge
    • GDC-0449
    • Hedgehog Antagonist GDC-0449
Experimental
Subprotocol U (NF2 inactivating mutation)
Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Defactinib
    Given PO
  • Drug: Defactinib Hydrochloride
    Given PO
    Other names:
    • PF-04554878
    • VS-6063
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib malate PO QD for 4 weeks. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Sunitinib Malate
    Given PO
    Other names:
    • SU011248
    • SU11248
    • sunitinib
    • Sutent
Experimental
Subprotocol W (FGFR pathway aberrations)
Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: FGFR Inhibitor AZD4547
    Given PO
    Other names:
    • AZD4547
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol X (DDR2 S768R, I638F, or L239R mutation)
Patients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Dasatinib
    Given PO
    Other names:
    • BMS-354825
    • Dasatinib Hydrate
    • Dasatinib Monohydrate
    • Sprycel
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Y (Akt mutation)
Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Capivasertib
    Given PO
    Other names:
    • AZD5363
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
Patients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Binimetinib
    Given PO
    Other names:
    • ARRY-162
    • ARRY-438162
    • MEK162
    • Mektovi
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
Patients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Palbociclib
    Given PO
    Other names:
    • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
    • Ibrance
    • PD 0332991
    • PD 332991
    • PD 991
    • PD-0332991
Experimental
Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)
Patients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Palbociclib
    Given PO
    Other names:
    • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
    • Ibrance
    • PD 0332991
    • PD 332991
    • PD 991
    • PD-0332991
Experimental
Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Biological: Nivolumab
    Given IV
    Other names:
    • BMS-936558
    • MDX-1106
    • NIVO
    • ONO-4538
    • Opdivo
Experimental
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Larotrectinib
    Given PO
    Other names:
    • ARRY 470
    • LOXO 101
    • LOXO-101
  • Drug: Larotrectinib Sulfate
    Given PO
    Other names:
    • ARRY 470 Sulfate
    • LOXO 101 Sulfate
    • LOXO-101 Sulfate
    • Vitrakvi
Experimental
Subprotocol Z1F (PIK3CA mutation)
Patients with PIK3CA mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Copanlisib
    Given IV
    Other names:
    • BAY 80-6946
    • PI3K Inhibitor BAY 80-6946
  • Drug: Copanlisib Hydrochloride
    Given IV
    Other names:
    • 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2)
    • Aliqopa
    • BAY 80-6946 Dihydrochloride
    • BAY-80-6946 Dihydrochloride
    • Copanlisib Dihydrochloride
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1G (PTEN loss)
Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Copanlisib
    Given IV
    Other names:
    • BAY 80-6946
    • PI3K Inhibitor BAY 80-6946
  • Drug: Copanlisib Hydrochloride
    Given IV
    Other names:
    • 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2)
    • Aliqopa
    • BAY 80-6946 Dihydrochloride
    • BAY-80-6946 Dihydrochloride
    • Copanlisib Dihydrochloride
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1H (PTEN mutation)
Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Copanlisib
    Given IV
    Other names:
    • BAY 80-6946
    • PI3K Inhibitor BAY 80-6946
  • Drug: Copanlisib Hydrochloride
    Given IV
    Other names:
    • 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2)
    • Aliqopa
    • BAY 80-6946 Dihydrochloride
    • BAY-80-6946 Dihydrochloride
    • Copanlisib Dihydrochloride
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Drug: Adavosertib
    Given PO
    Other names:
    • AZD-1775
    • AZD1775
    • MK-1775
    • MK1775
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1K (AKT mutation)
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Drug: Ipatasertib
    Given PO
    Other names:
    • GDC-0068
    • RG-7440
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
Experimental
Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)
Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other names:
    • Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Ulixertinib
    Give PO
    Other names:
    • BVD-523
    • VRT752271

Recruiting Locations

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
Contact:
Site Public Contact
205-934-0220
tmyrick@uab.edu

More Details

Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the biopsy material for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo collection of blood samples for research purposes. STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 37 treatment subprotocols based on molecularly-defined subgroup. (See Arms Section) STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step treatment or who could not tolerate the assigned treatment undergo review of their previous biopsy results to determine if another treatment is available or undergo another biopsy. Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy. STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and collection of blood samples for research purposes. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.