Purpose

The purpose of the study is to learn from the real world practice of prescribing targeted therapies to patients with advanced cancer whose tumor harbors a genomic variant known to be a drug target or to predict sensitivity to a drug. NOTE: Due to character limits, the arms section does NOT include all TAPUR Study relevant biomarkers. For additional information, contact TAPUR@asco.org, or if a patient, your nearest participating TAPUR site (see participating centers). ********************************************************************************************* ********************************************************************************* Results in publication or poster presentation format are posted as they become available for individual cohorts at www.tapur.org/news. The results may be accessed at any time. All results will be made available on clinicaltrials.gov at the end of the study. Indexing of available results on PubMed is in progress. ********************************************************************************************* *********************************************************************************

Conditions

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 12 years of age or older (*Restrictions apply. Not all therapies are available for patients <18) - Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer treatment or for whom, in the opinion of the treating physician, no such treatment is available or indicated - Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria) - Patients must have acceptable organ function as defined below. However, as noted above, drug-specific inclusion/

Exclusion Criteria

specified in the protocol appendix for each agent will take precedence for this and all inclusion criteria: 1. Absolute neutrophil count ≥ 1.5 x 106/µl 2. Hemoglobin > 9.0 g/dl 3. Platelets > 75,000/µl 4. Total bilirubin < 2.0 mg/ dl, except in patients with Gilbert's Syndrome 5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) < 2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with known hepatic metastases) 6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50 mL/min/1.73 m2 - Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor, Lugano criteria for non Hodgkin lymphoma or International Myeloma Working Group criteria for multiple myeloma), defined, as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or a subcutaneous or superficial lesion that can be measured with calipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable disease by physical or radiographic examination but do not meet these definitions of measurable disease are eligible and will be considered to have evaluable disease. Patient's whose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only) are NOT eligible - Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited or New York State accredited (for labs offering services to residents of NY) laboratory that has registered the test with the National Institutes of Health (NIH) Genetic Test Registry or has established an integration with the TAPUR platform. The genomic or IHC test used to qualify a patient for participation in TAPUR may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed in a laboratory that meets the criteria described above. - Ability to understand and the willingness to sign a written informed consent/assent document - Have a tumor genomic profile for which single agent treatment with one of the FDA approved targeted anti-cancer drugs included in this study has potential clinical benefit based on the criteria described in protocol - For orally administered drugs, the patient must be able to swallow and tolerate oral medication and must have no known malabsorption syndrome - Because of the risks of drug treatment to the developing fetus, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for four months following completion of study therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or if she is the partner of a male participant in this study and becomes pregnant while he is participating in this study, she should inform her or her partner's treating physician immediately as well as her obstetrician. Female study patients who become pregnant must immediately discontinue treatment with any study therapy. Male patients should avoid impregnating a female partner. Male study patients, even if surgically sterilized, (i.e. post-vasectomy) must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or completely abstain from sexual intercourse Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have measurable and evaluable disease per RECIST v1.1 Exclusion Criteria: - Patients whose disease is not measurable or cannot be assessed by radiographic imaging or physical examination (e.g., elevated serum tumor marker only) are not eligible - Patients with primary brain tumors or leptomeningeal metastases are excluded - Patients with previously treated brain metastases are eligible, provided that the patient has not experienced a seizure or had a clinically significant change in neurological status within the 3 months prior to registration. All patients with previously treated brain metastases must be clinically stable for at least 1 month after completion of treatment and off steroid treatment for one month prior to study enrollment. - Patients with known progressive brain metastases are eligible but additional eligibility criteria apply Note: there are additional exclusion criteria that may apply

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Other
Group 3 (ALK, ROS1, MET)
Participants receive crizotinib - dosage, frequency and duration per label; acceptable genomic matches include ALK fusion or mutation, ROS1 fusion, MET amplification or mutation, MET exon 14 alteration, RON amplification or mutation
  • Drug: Crizotinib
    drug
    Other names:
    • Xalkori
Other
Group 4 (CDKN2A, CDK4, CDK6)
Participants receive palbociclib - dosage, frequency and duration per label; acceptable genomic matches include CDKN2A loss or mutation, CDK4, CDK6 amplifications
  • Drug: Palbociclib
    drug
    Other names:
    • Ibrance
Other
Group 5 (CSF1R,PDGFR,VEGFR)
Participants receive sunitinib - dosage, frequency and duration per label; acceptable genomic matches include CSF1R, PDGFR, VEGFR1/2/3, KIT, FLT-3, RET, FGFR1/2/3, VHL amplifications or mutations
  • Drug: Sunitinib
    drug
    Other names:
    • Sutent
Other
Group 6 (mTOR, TSC)
Participants receive temsirolimus - dosage, frequency and duration per label; acceptable genomic matches include mTOR, TSC1/2, AKT1 mutations
  • Drug: Temsirolimus
    drug
    Other names:
    • Torisel
Other
Group 8 (ERBB2)
Participants receive trastuzumab and pertuzumab - dosage, frequency and duration per label; acceptable genomic matches include ERBB2 amplification, overexpression, and specific mutations
  • Drug: Trastuzumab and Pertuzumab
    drug
    Other names:
    • Herceptin and Perjeta
Other
Group 9 (BRAF V600E/D/K/R)
Participants receive vemurafenib and cobimetinib - dosage, frequency and duration per label; acceptable genomic matches include BRAF V600E/D/K/R mutations
  • Drug: Vemurafenib and Cobimetinib
    drug
    Other names:
    • Zelboraf and Cotellic
Other
Group 13 (RET,VEGFR1/2/3,KIT,PDGFRβ,RAF-1,BRAF)
Participants receive regorafenib - dosage, frequency and duration per label; acceptable genomic matches include RET, VEGFR1/2/3, KIT, PDGFRβ, RAF-1, BRAF mutations or amplifications
  • Drug: Regorafenib
    drug
    Other names:
    • Stivarga
Other
Group 14 (BRCA1/2; ATM)
Participants receive olaparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 inactivating mutations; ATM mutations or deletions
  • Drug: Olaparib
    drug
    Other names:
    • Lynparza
Other
Group 15 (POLE, POLD1, high mutational load)
Participants receive pembrolizumab - dosage, frequency and duration per label; acceptable genomic matches include specific POLE and POLD1 mutations, tumor mutational burden as defined in protocol
  • Drug: Pembrolizumab
    drug
    Other names:
    • Keytruda
Other
Group 16 (MSI-H, high mutational load and others)
Participants receive nivolumab and ipilimumab - dosage, frequency and duration per label; acceptable genomic matches include MSI high status, high tumor mutational burden, MLH1, MSH2/6, PMS2, EPCAM mutations, specific POLE or POLD1 mutations, BRCA1/2, ATM, MSH3, PMS1, MLH3, EXO1, RFC1/2/3/4/5, PCNA, RPA1/2/3/4, and SSBP1 loss of function mutations
  • Drug: Nivolumab and Ipilimumab
    drug
    Other names:
    • Opdivo and Yervoy
Other
Group 17 (CDKN2A, CDK4, CDK6)
Participants receive abemaciclib - dosage, frequency and duration per label; acceptable genomic matches include CDKN2A loss or mutation, CDK4, CDK6 amplifications
  • Drug: Abemaciclib
    drug
    Other names:
    • Verzenio
Other
Group 18 (NRG1)
Participants receive afatinib - dosage, frequency and duration per label; acceptable genomic matches include NRG1 fusions
  • Drug: Afatinib
    drug
    Other names:
    • Gilotrif
Other
Group 19 (BRCA1/2, PALB2)
Participants receive Participants receive talazoparib - dosage, frequency and duration per label; acceptable genomic matches include germline or somatic BRCA1/2 and PALB2 mutations
  • Drug: Talazoparib
    drug
    Other names:
    • Talzenna

Recruiting Locations

University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama 35294
Contact:
Teresa Ross, RN, OCN
205-975-0103
tross@uabmc.edu

More Details

Status
Recruiting
Sponsor
American Society of Clinical Oncology

Study Contact

Pam Mangat, MS
www.tapur.org
pam.mangat@asco.org

Detailed Description

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a non-randomized clinical trial that aims to describe the safety and efficacy of commercially available, targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has a potentially actionable genomic variant. TAPUR will study Food and Drug Administration (FDA)-approved targeted therapies that are contributed by collaborating pharmaceutical companies, catalogue the choice of molecular profiling test by clinical oncologists and develop hypotheses for additional clinical trials.

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.