M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer

August 28, 2018 updated by: Momenta Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

128

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Center
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada, H2X 3J4
        • CHUM Hospital St-Luc
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham Comprehensive Cancer Center
      • Huntsville, Alabama, United States, 35805
        • Clearview Cancer Institute
    • Arizona
      • Tucson, Arizona, United States, 85715
        • Arizona Clinical Research Center
      • Tucson, Arizona, United States, 85719
        • University of Arizona
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado School of Medicine - Division of Medical Oncology
      • Fort Collins, Colorado, United States, 80528
        • Poudre Valley Health System
    • Connecticut
      • Meriden, Connecticut, United States, 06451
        • Hartford Healthcare Cancer Institute at Midstate Medical Center
    • Florida
      • Tampa, Florida, United States, 33613
        • Florida Hospital Tampa
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center
    • Illinois
      • Arlington Heights, Illinois, United States, 60005
        • Illinois Cancer Specialists
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Crescent City Research Consortium
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
    • Maryland
      • Towson, Maryland, United States, 21204
        • University of Maryland- St Joseph's Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Worcester, Massachusetts, United States, 01605
        • UMass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • St. Joseph Mercy Hospital
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro-Minnesota Community Clinical Oncology Program
    • Missouri
      • Kansas City, Missouri, United States, 64154
        • University of Kansas Cancer Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Cancer Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • Bronx, New York, United States, 10461
        • Montefiore-Einstein Center for Cancer Care
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97227
        • Northwest Cancer Specialists
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Hershey Cancer Center
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Cancer Center of the Carolinas/ITOR
    • Texas
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Sciences Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology, P.A.
      • Tyler, Texas, United States, 75702
        • Texas Oncology
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: nab-paclitaxel, gemcitabine, placebo

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.
Drug: nab-paclitaxel
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Names:
  • Abraxane (nab-paclitaxel)
Drug: gemcitabine
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Names:
  • Gemzar (gemcitabine)
Drug: placebo
Placebo will be dosed daily
Experimental: nab-paclitaxel, gemcitabine, necuparanib

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.
Drug: nab-paclitaxel
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Names:
  • Abraxane (nab-paclitaxel)
Drug: gemcitabine
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Names:
  • Gemzar (gemcitabine)
Drug: Necuparanib
Necuparanib will be dosed daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Safety
Time Frame: Part A: Baseline to 28 days after first-dose and end of study
At baseline and then each of 6 visits after the start of dosing in a 28-day treatment cycle, adverse event surveillance, liver function enzyme levels, WBC with differential, ANC, aPTT, and PT are measured. This is repeated for each 28 day treatment cycle until disease progression or end of treatment. A final assessment is performed 30 days post-final necuparanib dose.
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
Time in months from first dose of study medication until death
Time in months from first dose of study medication until death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: Maximum concentration of necuparanib
Time Frame: Baseline to 28 days after first dose.
One before and seven blood samples after the first dose followed by 5 additional lab draws, once at each of the 5 remaining visits in the first 28-day cycle.
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
Time in months from first dose of study drug until disease progression
Time from first dose of study drug until disease progression

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Momenta Pharmaceuticals, Inc.

Investigators

  • Study Director: James Roach, MD, Momenta Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

October 24, 2016

Study Completion (Actual)

October 24, 2016

Study Registration Dates

First Submitted

May 22, 2012

First Submitted That Met QC Criteria

June 15, 2012

First Posted (Estimate)

June 18, 2012

Study Record Updates

Last Update Posted (Actual)

August 29, 2018

Last Update Submitted That Met QC Criteria

August 28, 2018

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M402-103

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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