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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01621243
Recruitment Status : Terminated (The study was terminated after a pre-planned futility analyses showed an insufficient level of efficacy in the study population to warrant continuation.)
First Posted : June 18, 2012
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Momenta Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 22, 2012
First Posted Date  ICMJE June 18, 2012
Last Update Posted Date August 29, 2018
Study Start Date  ICMJE May 2012
Actual Primary Completion Date October 24, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2014)
  • 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 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 15, 2012)
Safety [ Time Frame: Baseline to 28 days after first dose and at end of study, estimated up to 180 days. ]
At baseline and then each of the 6 visits after the start of dosing in a 28-day treament cycle, adverse event surveillance, liver function enzyme levels, WBC with differential, ANC, aPTT, PT, and PF4 antibodies are measured. This is repeated for each 28-day treatment cycle for up to 6 treatment cycles.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2014)
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2012)
  • Maximum concentration of M402 [ 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.
  • Time to maximum concentration of anti-Factor Xa [ Time Frame: Baseline to 28 days after first dose. ]
    One sample will be taken before the first dose, once before dosing on Days 1, 2, 15, 16, and at the end of the first 28-day treatment cycle.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Cancer
Intervention  ICMJE
  • Drug: nab-paclitaxel
    nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
    Other Name: Abraxane (nab-paclitaxel)
  • Drug: gemcitabine
    gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
    Other Name: Gemzar (gemcitabine)
  • Drug: placebo
    Placebo will be dosed daily
  • Drug: Necuparanib
    Necuparanib will be dosed daily
Study Arms  ICMJE
  • 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.

    Interventions:
    • Drug: nab-paclitaxel
    • Drug: gemcitabine
    • Drug: placebo
  • 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.

    Interventions:
    • Drug: nab-paclitaxel
    • Drug: gemcitabine
    • Drug: Necuparanib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 4, 2016)
128
Original Estimated Enrollment  ICMJE
 (submitted: June 15, 2012)
160
Actual Study Completion Date  ICMJE October 24, 2016
Actual Primary Completion Date October 24, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01621243
Other Study ID Numbers  ICMJE M402-103
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Momenta Pharmaceuticals, Inc.
Study Sponsor  ICMJE Momenta Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: James Roach, MD Momenta Pharmaceuticals
PRS Account Momenta Pharmaceuticals, Inc.
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP