A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Minnelide™ Capsules Given Alone or in Combination With Protein-Bound Paclitaxel in Patients With Advanced Solid Tumors

Purpose

A Phase I, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of Minnelide™Capsules given daily for 21 days followed by 7 days off schedule in patients with Advanced Solid Tumors

Conditions

  • Advanced Cancer
  • Gastric Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer Metastatic
  • Colo-rectal Cancer
  • Solid Tumor
  • Solid Carcinoma
  • Solid Carcinoma of Stomach
  • Cancer of Stomach

Eligibility

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

Inclusion Criteria

  • Patients with histologically confirmed advanced solid tumors (regimen A) or breast or pancreas (regimen B)
  • Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy
  • Prior treatment with protein-bound paclitaxel allowed if it has been six months since received or progressed on protein-bound paclitaxel and plan to continue to receive protein-bound paclitaxel with MinnelideTMcapsules
  • One or more metastatic tumors measurable per RECIST Criteria
  • Karnofsky performance ≥ 70%
  • Life expectancy of at least 3 months
  • Age: 18 years
  • Signed, written IRB-approved informed consent
  • A negative pregnancy test (if female)
  • Acceptable liver function:
  • Bilirubin 1.5 times upper limit of normal
  • AST (SGOT), ALT (SGPT) and Alkaline phosphatase 2.5 times upper limit of normal (if liver metastases are present, then 5 x ULN is allowed)
  • Acceptable renal function:

o Serum creatinine within normal limits, OR calculated creatinine clearance 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

- Acceptable hematologic status:

- Granulocyte 1500 cells/mm3

- Platelet count 100,000 (plt/mm3)

- Hemoglobin 9 g/dL

- Urinalysis:

o No clinically significant abnormalities

- Acceptable coagulation status:

- PT ≤ 1.5 times institutional ULN

- PTT ≤ 1.5 times institutional ULN

- For men and women of child-producing potential, the use of effective contraceptive methods during the study

Exclusion Criteria

  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
  • Baseline QTc exceeding 450 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrythmic agents.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry (6 weeks for nitrosoureas or Mitomycin C).
  • Unwillingness or inability to comply with procedures required in this protocol
  • Known infection with HIV, hepatitis B, or hepatitis C
  • Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
  • Patients who are currently receiving any other investigational agent

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Regimen A (monotherapy)
Minnelide™Capsules given daily orally for 21 days followed by a 7 day rest period. One cycle will equal 28 days. This will be a dose escalation.
  • Drug: Minnelide™Capsules
    Minnelide™ is a water soluble disodium salt variant of triptolide an heat shock protein (HSP) inhibitor.
Experimental
Regimen B (combination)
Minnelide™Capsules given daily for 21 days followed by a 7 day rest period in combination with protein-bound paclitaxel given intravenously on day 2, 8 and 15 of a 28 day cycle. The dose of protein-bound paclitaxel will be 125mg/m2 on days 1, 8 and 15. The dose of Minnelide™Capsules will be determined by dose escalation.
  • Drug: Minnelide™Capsules
    Minnelide™ is a water soluble disodium salt variant of triptolide an heat shock protein (HSP) inhibitor.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35249
Contact:
205-934-9999

More Details

NCT ID
NCT03129139
Status
Recruiting
Sponsor
Minneamrita Therapeutics LLC

Study Contact

Cameron Wright, MS
6023588341
cwright@td2inc.com