A Phase 2 Study of BPM31510 (Ubidecarenone, USP) Nanosuspension Injection Administered Intravenously With Gemcitabine as 2nd/3rdline Therapy in Advanced Pancreatic Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 12
- 主要终点
- Treatment Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
BPM31510 plus gemcitabine
BPM31510 Nanosuspension Injection (40 mg/mL) starting dose of 110 mg/kg administered IV over 144 hours as 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday).
Starting on Day 21-treatment 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.
干预措施: BPM31510 Nanosuspension Injection (Drug)
BPM31510 plus gemcitabine
BPM31510 Nanosuspension Injection (40 mg/mL) starting dose of 110 mg/kg administered IV over 144 hours as 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday).
Starting on Day 21-treatment 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.
干预措施: Gemcitabine (Drug)
BPM31510 monotherapy
BPM31510 Nanosuspension Injection (40 mg/mL) starting dose of 110 mg/kg administered IV over 144 hours as 2 consecutive 72-hour infusions per week (Tuesday-Friday and Friday-Monday).
干预措施: BPM31510 Nanosuspension Injection (Drug)
结局指标
主要结局
Treatment Response
时间窗: 10 weeks (End of Cycle 2)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. (the appearance of new lesions is also considered progression); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR) = CR + PR
次要结局
- Overall Survival (OS)(Up to study completion, an average of 1 year)
- Time to Progression (TTP)(Day 1, End of Cycle 2 (10 weeks) and every 2 cycles (every 8 weeks) through study completion, an average of 1 year)
- Progression Free Survival (PFS)(Up to study completion, an average of 1 year)