Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Momenta Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01621243
First received: May 22, 2012
Last updated: August 4, 2016
Last verified: August 2016
  Purpose
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 Intervention Phase
Metastatic Pancreatic Cancer
Drug: nab-paclitaxel
Drug: gemcitabine
Drug: placebo
Drug: Necuparanib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Momenta Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 128
Study Start Date: May 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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
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 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: Necuparanib
Necuparanib will be dosed daily

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621243

  Show 37 Study Locations
Sponsors and Collaborators
Momenta Pharmaceuticals, Inc.
Investigators
Study Director: James Roach, MD Momenta Pharmaceuticals
  More Information

Responsible Party: Momenta Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01621243     History of Changes
Other Study ID Numbers: M402-103 
Study First Received: May 22, 2012
Last Updated: August 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Momenta Pharmaceuticals, Inc.:
necuparanib
gemcitabine
heparin
low molecular weight heparin
nab-Paclitaxel

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 30, 2016