M402 in Combination With Nab-Paclitaxel and Gemcitabine in Pancreatic Cancer
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Purpose
People with primary metastatic pancreatic cancer will be treated with nab-paclitaxel and gemcitabine in combination with an investigational agent called 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. M402 has been re-engineered from heparin to have much lower blood thinning activity while keeping the anti-tumor activity. The investigators are testing whether M402 administered in combination with nab-paclitaxel and gemcitabine may be more effective than nab-paclitaxel and gemcitabine.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Pancreatic Cancer |
Drug: nab-paclitaxel Drug: gemcitabine Drug: placebo Drug: M402 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
- Part A: Safety [ Time Frame: Part A: Baseline to 28 days after first-dose and end of study ] [ Designated as safety issue: Yes ]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 M402 dose.
- Part B: Overall Survival [ Time Frame: Time in months from first dose of study medication until death ] [ Designated as safety issue: Yes ]Time in months from first dose of study medication until death
- Part A: Maximum concentration of M402 [ Time Frame: Baseline to 28 days after first dose. ] [ Designated as safety issue: Yes ]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.
- Part B: Duration of progression-free survival [ Time Frame: Time from first dose of study drug until disease progression ] [ Designated as safety issue: Yes ]Time in months from first dose of study drug until disease progression
| Estimated Enrollment: | 180 |
| Study Start Date: | May 2012 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | January 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: nab-paclitaxel, gemcitabine, placebo
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
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Name: Abraxane (nab-paclitaxel)
Drug: gemcitabine
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Name: Gemzar (gemcitabine)
Drug: placebo
Placebo will be dosed daily
|
|
Experimental: nab-paclitaxel, gemcitabine, M402
Part A: Following a single-dose of M402 and a 7-day follow-up period, M402 will be 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 M402 only will proceed by cohort in a 3+3 design. Part B: A fixed dose of M402 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
nab-paclitaxel dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Name: Abraxane (nab-paclitaxel)
Drug: gemcitabine
gemcitabine will be dosed on Day 1, Day 8, Day 15 of each 28-day cycle
Other Name: Gemzar (gemcitabine)
Drug: M402
M402 will be dosed daily
|
Detailed Description:
Part A is an open-label, multiple ascending dose patient study of M402 given first as a single dose and then daily in combination with the nab-paclitaxel and gemcitabine regimen. It will be conducted to evaluate the safety and tolerability of M402 alone and in combination with nab-paclitaxel and gemcitabine and to recommend an M402 dose regimen for subsequent evaluation in Part B. Part B is a randomized, double-blind study investigating the antitumor activity of M402 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. Only Part A is currently open.
Part A - Primary Objectives:
- To evaluate the safety and tolerability of M402 in combination with nab-paclitaxel and gemcitabine.
- To determine the dose of M402 to be carried forward into Part B.
Part B - Primary Objective:
To evaluate overall survival in patients treated with M402 + nab-paclitaxel + gemcitabine compared with placebo + nab-paclitaxel + gemcitabine.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
- Brain metastasis or active second malignancy
- 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
- Used NSAIDs, ASA (except ≤ 81 mg) for at least 10 days of the preceding 14 days before screening
- 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
Contacts and Locations| Contact: Lacey Chance, BS | 303 722 7768 | lchance@ockham.com |
| United States, Massachusetts | |
| Massachusetts General Hospital | Not yet recruiting |
| Boston, Massachusetts, United States, 02114 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| United States, Ohio | |
| Gabrail Cancer Center | Not yet recruiting |
| Canton, Ohio, United States, 44718 | |
| United States, South Carolina | |
| Institute of Translational Oncology Research | Not yet recruiting |
| Greenville, South Carolina, United States, 29605 | |
| United States, Texas | |
| University of Texas Health Sciences Center | Not yet recruiting |
| San Antonio, Texas, United States, 78229 | |
More Information
No publications provided
| Responsible Party: | Momenta Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT01621243 History of Changes |
| Other Study ID Numbers: | M402-103 |
| Study First Received: | May 22, 2012 |
| Last Updated: | May 9, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Momenta Pharmaceuticals, Inc.:
|
gemcitabine M402 heparin low molecular weight heparin nab-Paclitaxel |
Additional relevant MeSH terms:
|
Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Heparin, Low-Molecular-Weight Gemcitabine Paclitaxel Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions |
Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents Antimetabolites, Antineoplastic Antimetabolites Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents Tubulin Modulators |
ClinicalTrials.gov processed this record on May 16, 2013