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

NCT ID: NCT01621243

Last Updated: 2018-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2016-10-24

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Metastatic Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

nab-paclitaxel

Intervention Type DRUG

nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle

gemcitabine

Intervention Type DRUG

gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle

placebo

Intervention Type DRUG

Placebo will be dosed daily

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.

Group Type EXPERIMENTAL

nab-paclitaxel

Intervention Type DRUG

nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle

gemcitabine

Intervention Type DRUG

gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle

Necuparanib

Intervention Type DRUG

Necuparanib will be dosed daily

Interventions

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nab-paclitaxel

nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle

Intervention Type DRUG

gemcitabine

gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle

Intervention Type DRUG

placebo

Placebo will be dosed daily

Intervention Type DRUG

Necuparanib

Necuparanib will be dosed daily

Intervention Type DRUG

Other Intervention Names

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Abraxane (nab-paclitaxel) Gemzar (gemcitabine)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Momenta Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Roach, MD

Role: STUDY_DIRECTOR

Momenta Pharmaceuticals

Locations

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University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Site Status

Clearview Cancer Institute

Huntsville, Alabama, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

University of Colorado School of Medicine - Division of Medical Oncology

Aurora, Colorado, United States

Site Status

Poudre Valley Health System

Fort Collins, Colorado, United States

Site Status

Hartford Healthcare Cancer Institute at Midstate Medical Center

Meriden, Connecticut, United States

Site Status

Florida Hospital Tampa

Tampa, Florida, United States

Site Status

Southeastern Regional Medical Center

Newnan, Georgia, United States

Site Status

Illinois Cancer Specialists

Arlington Heights, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Crescent City Research Consortium

Marrero, Louisiana, United States

Site Status

Ochsner Medical Center

New Orleans, Louisiana, United States

Site Status

University of Maryland- St Joseph's Medical Center

Towson, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Umass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Karmanos Cancer Center

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Metro-Minnesota Community Clinical Oncology Program

Saint Louis Park, Minnesota, United States

Site Status

University of Kansas Cancer Center

Kansas City, Missouri, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Montefiore-Einstein Center for Cancer Care

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Northwest Cancer Specialists

Portland, Oregon, United States

Site Status

Penn State Hershey Cancer Center

Hershey, Pennsylvania, United States

Site Status

Cancer Center of the Carolinas/ITOR

Greenville, South Carolina, United States

Site Status

University of Texas Health Sciences Center

San Antonio, Texas, United States

Site Status

Texas Oncology, P.A.

Tyler, Texas, United States

Site Status

Texas Oncology

Tyler, Texas, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

The Ottawa Hospital Cancer Center

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

CHUM Hospital St-Luc

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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O'Reilly EM, Barone D, Mahalingam D, Bekaii-Saab T, Shao SH, Wolf J, Rosano M, Krause S, Richards DA, Yu KH, Roach JM, Flaherty KT, Ryan DP. Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma. Eur J Cancer. 2020 Jun;132:112-121. doi: 10.1016/j.ejca.2020.03.005. Epub 2020 Apr 28.

Reference Type DERIVED
PMID: 32361265 (View on PubMed)

O'Reilly EM, Roach J, Miller P, Yu KH, Tjan C, Rosano M, Krause S, Avery W, Wolf J, Flaherty K, Nix D, Ryan DP. Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Necuparanib Combined with Nab-Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results. Oncologist. 2017 Dec;22(12):1429-e139. doi: 10.1634/theoncologist.2017-0472. Epub 2017 Nov 20.

Reference Type DERIVED
PMID: 29158367 (View on PubMed)

Other Identifiers

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M402-103

Identifier Type: -

Identifier Source: org_study_id

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