BPM31510 Administered Intravenously With Gemcitabine in Advanced Pancreatic Cancer Patients

Study Overview
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Brief Summary
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This is a Phase 2 multicenter, open-label, non-randomized study to examine the safety and effectiveness of BPM31510 administered over 144-hours (two 72-hour 110mg/Kg doses) continuous intravenous (IV) infusion in combination with gemcitabine in advanced pancreatic cancer patients as 2nd / 3rd line therapy. The study will enroll up to 25 patients in the US and Europe.

Detailed Description
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This is a Phase 2 multicenter, open-label, non-randomized study to examine the safety and effectiveness of BPM31510 administered over 144-hours (two 72-hour 110mg/Kg doses) continuous intravenous (IV) infusion in combination with gemcitabine in advanced pancreatic cancer patients as 2nd / 3rd line therapy. Cycle 1 of therapy is 6 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 6 weeks plus gemcitabine administered on Mondays, Days 21, 28 and 35. Cycles 2-12 are 4 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 4 weeks plus gemcitabine administered on Mondays, Days 7, 14 and 21. Response will be assessed after Cycle 2 (10 weeks) and patients who continue onto Cycles 2-12 will be assessed every 2 cycles (8 weeks). Patients will continue BPM31510 in combination with gemcitabine, for a maximum of 12 cycles in the absence of intolerable toxicity and progression. If gemcitabine is discontinued due to chemotherapy-related toxicity, patients may continue to receive BPM31510 as monotherapy. Patients who experience disease progression but are, in the opinion of the investigator, receiving clinical benefit may continue BPM31510 as a monotherapy or in combination with gemcitabine or as a monotherapy pending approval from the Sponsor.

Official Title
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A Phase 2 Study of BPM31510 (Ubidecarenone, USP) Nanosuspension Injection Administered Intravenously With Gemcitabine as 2nd/3rdline Therapy in Advanced Pancreatic Cancer Patients

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: BPM31510 Nanosuspension Injection
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. The patient has undergone at least one prior, but no more than 2 prior standard, therapies for pancreatic cancer.If the patient has had prior gemcitabine treatment, the last date of gemcitabine administration-should be > 3 months prior to screening for the study. All patients who have previously received gemcitabine should be discussed with the medical monitor during screening The patient is at least 18 years old. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status Measurable tumor lesions according to RECIST 1.1 criteria (Section 10.2). In the opinion of the Investigator, the patient has a life expectancy of > 3 months. Sexually active patients and their partners agree to use an accepted method of contraception during the course of the study (Appendix C:Guidelines Regarding Women of Childbearing Potential). Female patients of childbearing potential must have a negative pregnancy test within 1 week prior to beginning study treatment. The patient has adequate organ and marrow function as follows: absolute Neutrophil Count (ANC) ≥ 1500 mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL, serum creatinine < upper limit of normal (ULN); total bilirubin < 1.5 X (ULN) ; alanine aminotransferase (ALT), aspartate transaminase (AST) ≤ 2.5 times the upper limit of normal (ULN) if no liver involvement or ≤ 5 times the upper limit of normal with liver involvement. The patient has serum electrolytes (including calcium, magnesium, phosphorous, sodium and potassium) within normal limits (supplementation to maintain normal electrolytes is allowed). The patient has adequate coagulation: prothrombin time (PT) and an International Normalized Ratio (INR), and partial thromboplastin time (PTT) ≤ 1.5 times the upper limit of normal (ULN), In the opinion of the Investigator, the patient is capable of understanding and complying with the protocol and has signed the informed consent document. Exclusion Criteria: The patient has uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. The patient has active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV). The patient has received chemotherapy or radiotherapy within 4 weeks or has received nitrosoureas or mitomycin C within 6 weeks prior to the first dose of study drug. The patient has received radiation to ≥ 25% of his or her bone marrow within 4 weeks of the first dose of study drug. The patient has received an investigational drug within 30 days of the first dose of study drug. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 4 weeks of Screening Visit). History of other malignancies (except adequately treated Stage 1 cancer, cured basal cell carcinoma, superficial bladder cancer, Breast ductal carcinoma in situ (DCIS), or carcinoma in situ of the cervix) unless documented free of cancer for ≥5 years. The patient has not recovered to grade ≤ 1 from adverse events (AEs) due to investigational drugs or other medications, which were administered more than 4 weeks prior to the first dose of study drug. The patient is pregnant or lactating. The patient is known to be positive for the human immunodeficiency virus (HIV). The effect of BPM31510 on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study. The patient has an inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator or designee. The patient is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids. The patient has uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding. The patient has a known predisposition for bleeding such as von Willebrand's disease or other such condition. The patient requires therapeutic doses of any anticoagulant, including low molecular weight heparin (LMWH). Concomitant use of warfarin, even at prophylactic doses, is prohibited.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BPM31510 plus gemcitabine<br>BPM31510 Nanosuspension Injection (40 mg/mL) will be administered IV over 144 hours at the starting dose of 110 mg/kg. Each patient will receive 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday). The patient will be subsequently treated with gemcitabine IV once weekly at a starting dose of 1000 mg/m2. Cycle 1 of combination therapy is 6 weeks in duration for patients with BPM31510 administered twice weekly on Tuesdays and Fridays for 6 weeks and gemcitabine administered on Mondays, Days 21, 28 and 35. Cycles 2-12 are 4 weeks in duration with BPM31510 administered twice weekly on Tuesdays and Fridays for 4 weeks and gemcitabine administered on Mondays, Days 7, 14 and 21. | Drug: BPM31510 Nanosuspension Injection<br> <br> * Other names: Ubidecarenone, USP;Drug: Gemcitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate is evaluated in patients treated with the combination of BPM31510 with gemcitabine. Tumor response of Partial Response (PR) or better, based on RECIST 1.1 criteria, will be assessed after Cycle 2 (10 weeks) and all patients who continue onto Cycles 2-12 will be assessed every 2 cycles (8 weeks). | Up to study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival is defined as the number of days from the first dose of study drug to the date of death due to any cause. | Up to study completion, an average of 1 year | 
| Time to Progression (TTP) | Time to Progression is defined as tumor progression measured from the first dose of study drug to the first documentation of progression. | Day 1, End of Cycle 2 (10 weeks) and every 2 cycles (every 8 weeks) through study completion, an average of 1 year | 
| Toxicity profile of BPM31510 + gemcitabine (CTCAE v4.02) | The toxicity profile of BPM31510 in combination with gemcitabine when administered as a 144-hour intravenous (IV) infusion in patients with advanced pancreatic cancer. Toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.02). | Every week through study completion, an average of 1 year | 
| Change in CA 19-9 levels | Evaluate the change in CA 19-9 levels in patients treated with BPM31510 in combination with gemcitabine when administered as a 144-hour intravenous (IV) infusion in patients with advanced pancreatic cancer. | Every month through study completion, an average of 1 year | 
| Progression Free Survival (PFS) | The number of days from the first dose of study drug to the first documentation of progression or death due to any cause. | 3 months (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Advanced Pancreatic Cancer