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

Sponsor
Momenta Pharmaceuticals, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT01621243
Collaborator
(none)
128
Enrollment
37
Locations
2
Arms
53.8
Duration (Months)
3.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
128 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Study Start Date :
May 1, 2012
Actual Primary Completion Date :
Oct 24, 2016
Actual Study Completion Date :
Oct 24, 2016

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Part A: Safety [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.

    2. Part B: Overall Survival [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

    1. Part A: Maximum concentration of necuparanib [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.

    2. Part B: Duration of progression-free survival [Time from first dose of study drug until disease progression]

      Time in months from first dose of study drug until disease progression

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Momenta Pharmaceuticals, Inc.

    Investigators

    • Study Director: James Roach, MD, Momenta Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Momenta Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01621243
    Other Study ID Numbers:
    • M402-103
    First Posted:
    Jun 18, 2012
    Last Update Posted:
    Aug 29, 2018
    Last Verified:
    Jan 1, 2017
    Keywords provided by Momenta Pharmaceuticals, Inc.
    necuparanib
    gemcitabine
    heparin
    low molecular weight heparin
    nab-Paclitaxel
    Additional relevant MeSH terms:
    Pancreatic Neoplasms
    Gemcitabine
    Paclitaxel
    Albumin-Bound Paclitaxel

    Study Results

    No Results Posted as of Aug 29, 2018