Minnelide Capsules and Protein-Bound Paclitaxel in Advanced Solid Tumors

What is the Purpose of this Study?

This study is designed to test an investigational drug called Minnelide in patients with cancer. Minnelide releases the active compound triptolide when exposed to the blood stream; laboratory experiments suggest that triptolide could be effective in killing tumor cells. There are two parts to the study: Regimen A and Regimen B. Regimen A focuses on patients who have cancer that has continued to grow despite treatment. Researchers aim to evaluate the safety and effects of Minnelide, as well as determine the dose that should be used in future studies and the best way to give the drug.

Regimen B focuses on patients who have pancreas or breast cancer that has continued to grow despite treatment. The study will evaluate Minnelide when given in combination with a drug called protein-bound paclitaxel. Researchers will determine the maximum dose of Minnelide that can be tolerated when given with protein-bound paclitaxel and whether it has any effect in patients with breast and/or pancreas cancer. While protein-bound paclitaxel is approved by the U.S. Food and Drug Administration for treatment of pancreas and breast cancer, it has not been approved for use in combination with Minnelide.

Eligibility

Inclusion:
Patients with histologically confirmed advanced solid tumors (regimen A), breast or pancreas (regimen B), or gastric cancer (regimen C)
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 MinnelideTM Capsules
One or more metastatic tumors measurable per RECIST v1.1 Criteria

Inclusion:
Patients with histologically confirmed advanced solid tumors (regimen A), breast or pancreas (regimen B), or gastric cancer (regimen C)
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 MinnelideTM Capsules
One or more metastatic tumors measurable per RECIST v1.1 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)
Albumin ≥ 3.0 g/dL
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 470 msec (using the Bazett's formula) and/or patients receiving class 1A or class III antiarrhythmic 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
Patients who are on a prohibited medication (section 4.4.2).
Patients with biliary obstruction and/or biliary stent (Regimen B only)

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Where can I participate?

Cedars-Sinai Cancer at SOCC

More about this Clinical Trial

What is the full name of this clinical trial?

MINNELIDE101: 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

Study Details

Disease Type/Condition

Breast cancer

Principal Investigator

Mita, Monica

Co-Investigators

Alain Mita, Andrew Hendifar, Bobbie Jo Rimel, Edwin Posadas, Heather McArthur, Jun Gong, Ronald Natale, Sukhmani Padda

Age Group

Adult

Phase

IRB Number

Pro00049784

ClinicalTrials.gov ID

NCT03129139

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org