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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Momenta Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Momenta Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01621243
First received: May 22, 2012
Last updated: November 19, 2014
Last verified: November 2014

May 22, 2012
November 19, 2014
May 2012
December 2016   (final data collection date for primary outcome measure)
  • Part A: Safety [ Time Frame: Part A: Baseline to 28 days after first-dose and end of study ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Time in months from first dose of study medication until death
Safety [ Time Frame: Baseline to 28 days after first dose and at end of study, estimated up to 180 days. ] [ Designated as safety issue: Yes ]
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.
Complete list of historical versions of study NCT01621243 on ClinicalTrials.gov Archive Site
  • Part A: Maximum concentration of necuparanib [ Time Frame: Baseline to 28 days after first dose. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Time in months from first dose of study drug until disease progression
  • Maximum concentration of M402 [ Time Frame: Baseline to 28 days after first dose. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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.
Not Provided
Not Provided
 
M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Metastatic Pancreatic Cancer
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
March 2017
December 2016   (final data collection date for primary outcome measure)

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
  • Brain metastasis or active second malignancy
  • 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
  • Used NSAIDs, ASA (except ≤ 81 mg) for at least 10 days of the preceding 14 days before screening
  • 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
Both
18 Years and older
No
Contact: Mary Fons-Colvin 919-972-7303 mfcolvin@novellaclinical.com
Contact: Kristine Sterbenz 919-972-7227 ksterbenz@novellaclinical.com
United States
 
NCT01621243
M402-103
No
Momenta Pharmaceuticals, Inc.
Momenta Pharmaceuticals, Inc.
Not Provided
Not Provided
Momenta Pharmaceuticals, Inc.
November 2014

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