m402 in combination with nab-paclitaxel and gemcitabine in pancreatic cancer

Conditions: Metastatic Pancreatic Cancer

Summary: people with primary metastatic pancreatic cancer will be treated with nab-paclitaxel and gemcitabine in combination with an investigational agent called necuparanib (m402). it is made from heparin, which is a well known blood thinner. blood thinners have been shown in prior animal and human studies to have anti-cancer effects. necuparanib has been re-engineered from heparin to have much lower blood thinning activity while keeping the anti-tumor activity. the investigators are testing whether necuparanib administered in combination with nab-paclitaxel and gemcitabine may be more effective than nab-paclitaxel and gemcitabine.

part a was an open-label, multiple ascending dose patient study of necuparanib given first as a single dose and then daily in combination with the nab-paclitaxel and gemcitabine regimen. it was conducted to evaluate the safety and tolerability of necuparanib alone and in combination with nab-paclitaxel and gemcitabine and to recommend a necuparanib dose regimen for subsequent evaluation in part b. part b is a randomized, double-blind study investigating the antitumor activity of necuparanib in combination with nab-paclitaxel and gemcitabine compared with nab-paclitaxel, gemcitabine, and placebo. in both parts a and b, a treatment period consists of one 28-day cycle. the study patient and investigator can decide to continue with additional 28-day cycles according to the patient's status at the end of each 28-day cycle. part a has completed enrollment and part b is currently open. part a - primary objectives: * to evaluate the safety and tolerability of necuparanib in combination with nab-paclitaxel and gemcitabine. * to determine the dose of necuparanib to be carried forward into part b. part b - primary objective: to evaluate overall survival in patients treated with necuparanib + nab-paclitaxel + gemcitabine compared with placebo + nab-paclitaxel + gemcitabine.

Eligibility criteria:
inclusion criteria: * age of 18 years or older * confirmed pancreatic ductal adenocarcinoma * metastatic disease as documented by ct scan or mri (locally advanced disease only not eligible) * at least 1 site of disease measurable by recist ver1.1 * ecog performance status of 0 to 1 * adequate bone marrow, renal capacity and hepatic function * willing to administer daily subcutaneous injections at home exclusion criteria: * any prior radiotherapy, chemotherapy, surgery, or investigational therapy for adjuvant or metastatic pancreatic cancer * history of suspected history, or presence of heparin induced toxicity (w/ or w/o thrombosis) * history of unexplained bleeding episodes within 3 months of m402 dosing * received thrombolytic agents w/in the previous month * had full-dose anticoagulation with heparin, enoxaparin, dalteparin, other lmwh, a/or other anticoagulants w/in 90 days before first dose of m402 * high cardiovascular risk, including but not limited to, recent coronary stenting or myocardial infarction in the past year * major trauma or surgery w/in prior 4 weeks

Keywords: necuparanib gemcitabine heparin low molecular weight heparin nab-paclitaxel