Overview

This trial is active, not recruiting.

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 August 2016.
Information provided to ClinicalTrials.gov by Momenta Pharmaceuticals, Inc..
Location data was received from the National Cancer Institute and was last updated in August 2016.