Clinical trial NCT02650804: BPM31510 Administered Intravenously With Gemcitabine in Advanced Pancreatic Cancer Patients
Official title: A Phase 2 Study of BPM31510 (Ubidecarenone, USP) Nanosuspension Injection Administered Intravenously With Gemcitabine as 2nd/3rdline Therapy in Advanced Pancreatic Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Cancer
Advanced Pancreatic Cancer
Lead sponsor: BPGbio
Sponsor class: INDUSTRY
First posted: 2016-01-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Phase 2 multicenter, open-label, non-randomized to examine safety, effectiveness of combination of BPM31510 administered as 144-hour continuous intravenous (IV) infusion with gemcitabine in advanced pancreatic cancer patients as 2nd line therapy. Cycle 1 combination 6 weeks in duration for patients with BPM31510 administered twice wk. for 6 wk. and gemcitabine administered Days 21, 28 and 35. Cycles 2-12 are 4 wk. in duration with BPM31510 administered twice wk. for 4 wk. and gemcitabine administered Days 7, 14 and 21.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Response
timeFrame: 10 weeks (End of Cycle 2)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to study completion, an average of 1 year
measure: Time to Progression (TTP)
timeFrame: Day 1, End of Cycle 2 (10 weeks) and every 2 cycles (every 8 weeks) through study completion, an average of 1 year
measure: Progression Free Survival (PFS)
timeFrame: Up to study completion, an average of 1 year
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Gilroy
country: United States
facility: Global Cancer Research Institute, Inc.
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Morristown
country: United States
facility: Atlantic Health System Morristown Medical Center
state: New Jersey
city: Bethlehem
country: United States
facility: Vita Medical Associates, P.C.
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
state: Strathclyde
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
Study officials:
affiliation: Mayo Clinic
name: Ramesh K Ramanathan, MD
role: PRINCIPAL_INVESTIGATOR
References: