Clinical trial NCT01621243: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: necuparanib
gemcitabine
heparin
low molecular weight heparin
nab-Paclitaxel
Lead sponsor: Momenta Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-06-18
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part A: Safety
timeFrame: Part A: Baseline to 28 days after first-dose and end of study
measure: Part B: Overall Survival
timeFrame: Time in months from first dose of study medication until death
Secondary outcomes:
measure: Part A: Maximum concentration of necuparanib
timeFrame: Baseline to 28 days after first dose.
measure: Part B: Duration of progression-free survival
timeFrame: Time from first dose of study drug until disease progression
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado School of Medicine - Division of Medical Oncology
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Health System
state: Colorado
city: Meriden
country: United States
facility: Hartford Healthcare Cancer Institute at Midstate Medical Center
state: Connecticut
city: Tampa
country: United States
facility: Florida Hospital Tampa
state: Florida
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Marrero
country: United States
facility: Crescent City Research Consortium
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Towson
country: United States
facility: University of Maryland- St Joseph's Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: Umass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota Community Clinical Oncology Program
state: Minnesota
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore-Einstein Center for Cancer Care
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Center of the Carolinas/ITOR
state: South Carolina
city: San Antonio
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM Hospital St-Luc
state: Quebec
Study officials:
affiliation: Momenta Pharmaceuticals
name: James Roach, MD
role: STUDY_DIRECTOR
References:
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.
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.