M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
- Conditions
- Metastatic Pancreatic Cancer
- Interventions
- Registration Number
- NCT01621243
- Lead Sponsor
- Momenta Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 128
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description nab-paclitaxel, gemcitabine, placebo nab-paclitaxel 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. nab-paclitaxel, gemcitabine, placebo 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. nab-paclitaxel, gemcitabine, necuparanib nab-paclitaxel 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. nab-paclitaxel, gemcitabine, placebo gemcitabine 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. nab-paclitaxel, gemcitabine, necuparanib gemcitabine 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. nab-paclitaxel, gemcitabine, necuparanib 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.
- Primary Outcome Measures
Name Time Method 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.
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
Name Time Method 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.
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
Trial Locations
- Locations (37)
Metro-Minnesota Community Clinical Oncology Program
🇺🇸Saint Louis Park, Minnesota, United States
Illinois Cancer Specialists
🇺🇸Arlington Heights, Illinois, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Crescent City Research Consortium
🇺🇸Marrero, Louisiana, United States
Texas Oncology, P.A.
🇺🇸Tyler, Texas, United States
Poudre Valley Health System
🇺🇸Fort Collins, Colorado, United States
Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Arizona Clinical Research Center
🇺🇸Tucson, Arizona, United States
Penn State Hershey Cancer Center
🇺🇸Hershey, Pennsylvania, United States
Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Missouri, United States
Cancer Center of the Carolinas/ITOR
🇺🇸Greenville, South Carolina, United States
The Ottawa Hospital Cancer Center
🇨🇦Ottawa, Ontario, Canada
Hartford Healthcare Cancer Institute at Midstate Medical Center
🇺🇸Meriden, Connecticut, United States
Montefiore-Einstein Center for Cancer Care
🇺🇸Bronx, New York, United States
Texas Oncology
🇺🇸Tyler, Texas, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
CHUM Hospital St-Luc
🇨🇦Montreal, Quebec, Canada
University of Maryland- St Joseph's Medical Center
🇺🇸Towson, Maryland, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
University of Texas Health Sciences Center
🇺🇸San Antonio, Texas, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Northwest Cancer Specialists
🇺🇸Portland, Oregon, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Umass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University of Colorado School of Medicine - Division of Medical Oncology
🇺🇸Aurora, Colorado, United States
St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Florida Hospital Tampa
🇺🇸Tampa, Florida, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States