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.
Brief Title
M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Metastatic Pancreatic Cancer
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
necuparanib
gemcitabine
heparin
low molecular weight heparin
nab-Paclitaxel
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01621243
Org Class
Industry
Org Full Name
Momenta Pharmaceuticals, Inc.
Org Study Id
M402-103
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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.
Outcome Measure
Part A: Safety
Outcome Time Frame
Part A: Baseline to 28 days after first-dose and end of study
Outcome Description
Time in months from first dose of study medication until death
Outcome Measure
Part B: Overall Survival
Outcome Time Frame
Time in months from first dose of study medication until death
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Baseline to 28 days after first dose.
Outcome Measure
Part A: Maximum concentration of necuparanib
Outcome Description
Time in months from first dose of study drug until disease progression
Outcome Time Frame
Time from first dose of study drug until disease progression
Outcome Measure
Part B: Duration of progression-free survival
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jennifer Chuy
Investigator Email
jchuy@montefiore.org
Investigator Phone