Overview

This trial has been terminated.

Condition metastatic pancreatic cancer
Treatments nab-paclitaxel, gemcitabine, placebo, necuparanib
Phase phase 1/phase 2
Sponsor Momenta Pharmaceuticals, Inc.
Start date May 2012
End date December 2016
Trial size 128 participants
Trial identifier NCT01621243, M402-103

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Placebo Comparator)
Part A: Not applicable. Part B: nab-paclitaxel, gemcitabine, and placebo. Placebo administered daily along with nab-paclitaxel and gemcitabine administration on Day 1, Day 8, and Day 15 of each 28-day cycle.
nab-paclitaxel Abraxane (nab-paclitaxel)
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
gemcitabine Gemzar (gemcitabine)
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
placebo
Placebo will be dosed daily
(Experimental)
Part A: Following a single-dose of necuparanib and a 7-day follow-up period, necuparanib was administered daily along with nab-paclitaxel and gemcitabine administration on Day 1, Day 8, and Day 15 of each 28-day cycle. Dose escalation of necuparanib proceeded by cohort in a 3+3 design. Part B: A fixed dose of necuparanib will be administered daily along with nab-paclitaxel and gemcitabine administration on Day 1, Day 8, and Day 15 of each 28-day cycle.
nab-paclitaxel Abraxane (nab-paclitaxel)
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
gemcitabine Gemzar (gemcitabine)
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
necuparanib
Necuparanib will be dosed daily

Primary Outcomes

Measure
Part A: Safety
time frame: Part A: Baseline to 28 days after first-dose and end of study
Part B: Overall Survival
time frame: Time in months from first dose of study medication until death

Secondary Outcomes

Measure
Part A: Maximum concentration of necuparanib
time frame: Baseline to 28 days after first dose.
Part B: Duration of progression-free survival
time frame: Time from first dose of study drug until disease progression

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase I/II, Two-Part, Multicenter Study to Evaluate the Safety and Efficacy of M402 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2017.
Information provided to ClinicalTrials.gov by Momenta Pharmaceuticals, Inc..