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

Momenta Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Pancreatic Cancer

Treatments: Drug: placebo; Drug: Necuparanib; Drug: nab-paclitaxel; Drug: gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01621243

M402-103

Details and patient eligibility

About

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.

Full 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.

Enrollment: 128 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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128 participants in 2 patient groups, including a placebo group

nab-paclitaxel, gemcitabine, placebo

Placebo Comparator group

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.

Treatment:

Drug: gemcitabine

Drug: nab-paclitaxel

Drug: placebo

nab-paclitaxel, gemcitabine, necuparanib

Experimental group

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.

Treatment:

Drug: gemcitabine

Drug: nab-paclitaxel

Drug: Necuparanib