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

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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.

Study Description
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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
Metastatic Pancreatic Cancer Drug: nab-paclitaxel Drug: gemcitabine Drug: placebo Drug: Necuparanib 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
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Study Type : Interventional  (Clinical Trial)
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 2012
Actual Primary Completion Date : October 24, 2016
Actual Study Completion Date : October 24, 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01621243


Locations
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Sponsors and Collaborators
Momenta Pharmaceuticals, Inc.
Investigators
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Study Director: James Roach, MD Momenta Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Momenta Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01621243    
Other Study ID Numbers: M402-103
First Posted: June 18, 2012    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: January 2017
Keywords provided by Momenta Pharmaceuticals, Inc.:
necuparanib
gemcitabine
heparin
low molecular weight heparin
nab-Paclitaxel
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Digestive System Diseases
Endocrine System Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
 Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs