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

Metastatic Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01621243
• Other study ID #: M402-103
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 2012
• Est. completion date: October 24, 2016

Study information

• Verified date: January 2017
• Source: Momenta Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 128
• Est. completion date: October 24, 2016
• Est. primary completion date: October 24, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• nab-paclitaxel
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
• gemcitabine
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
• placebo
Placebo will be dosed daily
• Necuparanib
Necuparanib will be dosed daily

Locations

Country	Name	City	State
Canada	CHUM Hospital St-Luc	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Center	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	University of Colorado School of Medicine - Division of Medical Oncology	Aurora	Colorado
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore-Einstein Center for Cancer Care	Bronx	New York
United States	Ohio State University	Columbus	Ohio
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Poudre Valley Health System	Fort Collins	Colorado
United States	Cancer Center of the Carolinas/ITOR	Greenville	South Carolina
United States	Penn State Hershey Cancer Center	Hershey	Pennsylvania
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	University of Kansas Cancer Center	Kansas City	Missouri
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Crescent City Research Consortium	Marrero	Louisiana
United States	Loyola University Medical Center	Maywood	Illinois
United States	Hartford Healthcare Cancer Institute at Midstate Medical Center	Meriden	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Southeastern Regional Medical Center	Newnan	Georgia
United States	Northwest Cancer Specialists	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Metro-Minnesota Community Clinical Oncology Program	Saint Louis Park	Minnesota
United States	University of Texas Health Sciences Center	San Antonio	Texas
United States	Florida Hospital Tampa	Tampa	Florida
United States	University of Maryland- St Joseph's Medical Center	Towson	Maryland
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	University of Arizona	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas
United States	Texas Oncology, P.A.	Tyler	Texas
United States	Umass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Momenta Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 A: Baseline to 28 days after first-dose and end of study
Primary	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	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.	Baseline to 28 days after first dose.
Secondary	Part B: Duration of progression-free survival	Time in months from first dose of study drug until disease progression	Time from first dose of study drug until disease progression