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

NCT01621243 | Terminated Phase 1

• 1 other identifier: M402-103
• Study Type: interventional
• Target: 128
• Locations: 2 countries
• Sites: 37

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.

Conditions

Metastatic Pancreatic Cancer

Keywords

necuparanib; gemcitabine; heparin; low molecular weight heparin; nab-Paclitaxel

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Part A: Maximum concentration of necuparanib

  Baseline to 28 days after first dose.

• Part B: Duration of progression-free survival

  Time from first dose of study drug until disease progression

Study Arms (2)

nab-paclitaxel, gemcitabine, placebo

PLACEBO COMPARATOR

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; Drug: gemcitabine; Drug: placebo

nab-paclitaxel, gemcitabine, necuparanib

EXPERIMENTAL

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; Drug: gemcitabine; Drug: Necuparanib

Interventions

nab-paclitaxel DRUG

nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle

Also known as: Abraxane (nab-paclitaxel)

nab-paclitaxel, gemcitabine, necuparanib; nab-paclitaxel, gemcitabine, placebo

gemcitabine DRUG

gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle

Also known as: Gemzar (gemcitabine)

nab-paclitaxel, gemcitabine, necuparanib; nab-paclitaxel, gemcitabine, placebo

placebo DRUG

Placebo will be dosed daily

nab-paclitaxel, gemcitabine, placebo

Necuparanib DRUG

Necuparanib will be dosed daily

nab-paclitaxel, gemcitabine, necuparanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Momenta Pharmaceuticals, Inc.: lead

Study Sites (37)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Arizona Clinical Research Center

Tucson, Arizona, 85715, United States

Location

University of Arizona

Tucson, Arizona, 85719, United States

Location

University of Colorado School of Medicine - Division of Medical Oncology

Aurora, Colorado, 80045, United States

Location

Poudre Valley Health System

Fort Collins, Colorado, 80528, United States

Location

Hartford Healthcare Cancer Institute at Midstate Medical Center

Meriden, Connecticut, 06451, United States

Location

Florida Hospital Tampa

Tampa, Florida, 33613, United States

Location

Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Crescent City Research Consortium

Marrero, Louisiana, 70072, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

University of Maryland- St Joseph's Medical Center

Towson, Maryland, 21204, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Umass Memorial Medical Center

Worcester, Massachusetts, 01605, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48105, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro-Minnesota Community Clinical Oncology Program

Saint Louis Park, Minnesota, 55416, United States

Location

University of Kansas Cancer Center

Kansas City, Missouri, 64154, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore-Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Northwest Cancer Specialists

Portland, Oregon, 97227, United States

Location

Penn State Hershey Cancer Center

Hershey, Pennsylvania, 17033, United States

Location

Cancer Center of the Carolinas/ITOR

Greenville, South Carolina, 29605, United States

Location

University of Texas Health Sciences Center

San Antonio, Texas, 78229, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Texas Oncology

Tyler, Texas, 75702, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

The Ottawa Hospital Cancer Center

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

CHUM Hospital St-Luc

Montreal, Quebec, H2X 3J4, Canada

Location

Related Publications (2)

• 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.

  PMID: 32361265 DERIVED

• 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.

  PMID: 29158367 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• James Roach, MD

  Momenta Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2012
• First Posted: June 18, 2012
• Study Start: May 1, 2012
• Primary Completion: October 24, 2016
• Study Completion: October 24, 2016
• Last Updated: August 29, 2018

Record last verified: 2017-01

Locations

US (34); CA (3)