bpm31510 administered intravenously with gemcitabine in advanced pancreatic cancer patients

Conditions: Pancreatic Cancer

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.

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.

Keywords: cancer advanced pancreatic cancer