Back to resultsM402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
Primary Purpose
Metastatic Pancreatic Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
nab-paclitaxel
gemcitabine
placebo
Necuparanib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring necuparanib, gemcitabine, heparin, low molecular weight heparin, nab-Paclitaxel
Eligibility 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
Sites / Locations
- University of Alabama at Birmingham Comprehensive Cancer Center
- Clearview Cancer Institute
- Arizona Clinical Research Center
- University of Arizona
- University of Colorado School of Medicine - Division of Medical Oncology
- Poudre Valley Health System
- Hartford Healthcare Cancer Institute at Midstate Medical Center
- Florida Hospital Tampa
- Southeastern Regional Medical Center
- Illinois Cancer Specialists
- Loyola University Medical Center
- Crescent City Research Consortium
- Ochsner Medical Center
- University of Maryland- St Joseph's Medical Center
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Umass Memorial Medical Center
- St. Joseph Mercy Hospital
- Karmanos Cancer Center
- Mayo Clinic
- Metro-Minnesota Community Clinical Oncology Program
- University of Kansas Cancer Center
- University of New Mexico Cancer Center
- Montefiore-Einstein Center for Cancer Care
- Montefiore Medical Center
- Memorial Sloan Kettering Cancer Center
- Ohio State University
- Northwest Cancer Specialists
- Penn State Hershey Cancer Center
- Cancer Center of the Carolinas/ITOR
- University of Texas Health Sciences Center
- Texas Oncology, P.A.
- Texas Oncology
- University of Wisconsin Hospital and Clinics
- The Ottawa Hospital Cancer Center
- Sunnybrook Health Sciences Centre
- CHUM Hospital St-Luc
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
nab-paclitaxel, gemcitabine, placebo
nab-paclitaxel, gemcitabine, necuparanib
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Part A: Safety
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
Secondary Outcome Measures
Part A: Maximum concentration of necuparanib
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 in months from first dose of study drug until disease progression
Full Information
NCT ID
NCT01621243
First Posted
May 22, 2012
Last Updated
August 28, 2018
Sponsor
Momenta Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01621243
Brief Title
M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated after a pre-planned futility analyses showed an insufficient level of efficacy in the study population to warrant continuation.
Study Start Date
May 2012 (undefined)
Primary Completion Date
October 24, 2016 (Actual)
Study Completion Date
October 24, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Momenta Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Cancer
Keywords
necuparanib, gemcitabine, heparin, low molecular weight heparin, nab-Paclitaxel
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
nab-paclitaxel, gemcitabine, placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
nab-paclitaxel, gemcitabine, necuparanib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
nab-paclitaxel
Other Intervention Name(s)
Abraxane (nab-paclitaxel)
Intervention Description
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Other Intervention Name(s)
Gemzar (gemcitabine)
Intervention Description
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Placebo will be dosed daily
Intervention Type
Drug
Intervention Name(s)
Necuparanib
Intervention Description
Necuparanib will be dosed daily
Primary Outcome Measure Information:
Title
Part A: Safety
Description
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.
Time Frame
Part A: Baseline to 28 days after first-dose and end of study
Title
Part B: Overall Survival
Description
Time in months from first dose of study medication until death
Time Frame
Time in months from first dose of study medication until death
Secondary Outcome Measure Information:
Title
Part A: Maximum concentration of necuparanib
Description
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 Frame
Baseline to 28 days after first dose.
Title
Part B: Duration of progression-free survival
Description
Time in months from first dose of study drug until disease progression
Time Frame
Time from first dose of study drug until disease progression
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Roach, MD
Organizational Affiliation
Momenta Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Clearview Cancer Institute
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Arizona Clinical Research Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
University of Colorado School of Medicine - Division of Medical Oncology
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Poudre Valley Health System
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
Hartford Healthcare Cancer Institute at Midstate Medical Center
City
Meriden
State/Province
Connecticut
ZIP/Postal Code
06451
Country
United States
Facility Name
Florida Hospital Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Southeastern Regional Medical Center
City
Newnan
State/Province
Georgia
ZIP/Postal Code
30265
Country
United States
Facility Name
Illinois Cancer Specialists
City
Arlington Heights
State/Province
Illinois
ZIP/Postal Code
60005
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Crescent City Research Consortium
City
Marrero
State/Province
Louisiana
ZIP/Postal Code
70072
Country
United States
Facility Name
Ochsner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
University of Maryland- St Joseph's Medical Center
City
Towson
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Umass Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
St. Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Metro-Minnesota Community Clinical Oncology Program
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
University of Kansas Cancer Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64154
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Montefiore-Einstein Center for Cancer Care
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Northwest Cancer Specialists
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Penn State Hershey Cancer Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Cancer Center of the Carolinas/ITOR
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
University of Texas Health Sciences Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Texas Oncology, P.A.
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Texas Oncology
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
The Ottawa Hospital Cancer Center
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
CHUM Hospital St-Luc
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
32361265
Citation
O'Reilly EM, Barone D, Mahalingam D, Bekaii-Saab T, Shao SH, Wolf J, Rosano M, Krause S, Richards DA, Yu KH, Roach JM, Flaherty KT, Ryan DP. Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma. Eur J Cancer. 2020 Jun;132:112-121. doi: 10.1016/j.ejca.2020.03.005. Epub 2020 Apr 28.
Results Reference
derived
PubMed Identifier
29158367
Citation
O'Reilly EM, Roach J, Miller P, Yu KH, Tjan C, Rosano M, Krause S, Avery W, Wolf J, Flaherty K, Nix D, Ryan DP. Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Necuparanib Combined with Nab-Paclitaxel and Gemcitabine in Patients with Metastatic Pancreatic Cancer: Phase I Results. Oncologist. 2017 Dec;22(12):1429-e139. doi: 10.1634/theoncologist.2017-0472. Epub 2017 Nov 20.
Results Reference
derived
Learn more about this trial
M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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