Study of MM-398 With or Without 5-FU/LV, Versus 5-FU/LV in Patients With Metastatic Pancreatic Cancer (NAPOLI-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01494506
First received: December 14, 2011
Last updated: February 11, 2016
Last verified: February 2016
  Purpose
The study is an open label, randomized phase 3 study of MM-398 with or without 5-Fluorouracil (5-FU) and Leucovorin (also known as folinic acid), versus 5-FU and leucovorin in metastatic pancreatic cancer patients who have progressed on prior gemcitabine based therapy.

Condition Intervention Phase
Metastatic Pancreatic Cancer
Drug: MM-398
Drug: 5 Fluorouracil
Drug: Leucovorin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Phase 3 Study of MM-398, With or Without 5-Fluorouracil and Leucovorin, Versus 5 Fluorouracil and Leucovorin in Patients With Metastatic Pancreatic Cancer Who Have Failed Prior Gemcitabine-based Therapy

Resource links provided by NLM:


Further study details as provided by Merrimack Pharmaceuticals:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization to death; until the data cut off 14 Feb 2014. The maximum time in follow up was 25 months. ] [ Designated as safety issue: No ]

    Overall survival was the primary efficacy endpoint of the study and was defined as the time from the date of patient randomization to the date of death or the date the patient was last known to be alive. OS was summarized by Kaplan-Meier methodology for each treatment group. Pairwise treatment group comparisons were carried out using unstratified log rank analyses on the ITT population. Hazard ratio estimates are from Cox regression analysis.

    The comparison of Arm C is based only on patients who were randomized under the 3-arm version of the protocol. Consequently, the 5-FU+Leucovorin (Combo Therapy Comparison) group is a subset of all patients randomized to 5-FU+Leucovorin, which is the Mono Therapy Comparison control and contains patients randomized under both the 2-arm and 3-arm versions of the protocol.



Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: Randomization until disease progression or death from any cause; Until the data cut off of 14 Feb 2014. The maximum time in follow up was 25 months. ] [ Designated as safety issue: No ]

    Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the date of the last tumor assessment. Patients with two or more consecutive missing response assessments prior to a visit with documented progression (or death) were censored at the last date of tumor assessment when the patient was documented to be progression free. PFS was summarized using Kaplan-Meier methods.

    The comparison of Arm C is based only on patients who were randomized under the 3-arm version of the protocol. Consequently, the 5-FU+Leucovorin (Combo Therapy Comparison) group is a subset of all patients randomized to 5-FU+Leucovorin, which is the Mono Therapy Comparison control and contains patients randomized under both the 2-arm and 3-arm versions of the protocol.


  • Objective Response Rate [ Time Frame: Assessment every 6 weeks after initial response; Day 1 to data cut off of 14 Feb 2014; maximum time on study 25 months. ] [ Designated as safety issue: No ]
    The objective response rate was a secondary efficacy endpoint of the study and was defined by the percentage of patients in the study population with a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator. Best overall response was defined per RECIST (version 1.1) recorded from randomization until progression or end of study. RECIST (v 1.1) criteria does not require confirmation of response, but an additional, more stringent analysis was also conducted, with designation of CR (or PR) requiring confirmation of response at least 4 weeks following the initial assessment of CR (or PR). Stable disease (SD) required an assessment of SD at least 6 weeks after starting treatment. Subjects with insufficient data for response classification were classified as Not Evaluable for best overall response, and as a non-responder for objective response, in the ITT population. Treatment groups are as indicated for the primary outcome of OS.


Enrollment: 417
Study Start Date: November 2011
Study Completion Date: October 2015
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MM-398
MM-398 120 mg/m2 Q3W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 120 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 100 mg/ m2 of irinotecan free base.
Drug: MM-398

Arm A: MM-398 120 mg/m2 IV Q3W

Arm C: MM-398 80mg/m2 IV Q2W

Other Name: PEP02
Active Comparator: 5 Fluorouracil and Leucovorin IV
5 Fluorouracil and Leucovorin IV
Drug: 5 Fluorouracil

Arm B: 5 Fluorouracil 2000 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: 5 Fluorouracil 2400 mg/m2 IV every 2 weeks

Other Name: 5-FU
Drug: Leucovorin

Arm B: Leucovorin 200 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: Leucovorin 400 mg/m2 IV every 2 weeks

Other Name: Folinic Acid
Experimental: MM-398, 5-FU and Leucovorin
MM-398 80 mg/m2, 5-FU and Leucovorin Q2W IV. Note: The published dose of ONIVYDE was expressed as the irinotecan hydrochloride trihydrate until October 2015. It is now expressed as the irinotecan free base. Converting a dose based on irinotecan hydrochloride trihydrate to a dose based on irinotecan free base is accomplished by substituting the Molecular Weight of irinotecan hydrochloride trihydrate (677.19 g/mole) with the Molecular Weight of irinotecan free base (586.68 g/mole), which results in a conversion factor of 0.866. 80 mg/m2 dose of irinotecan hydrochloride trihydrate is equivalent to 70 mg/ m2 of irinotecan free base.
Drug: MM-398

Arm A: MM-398 120 mg/m2 IV Q3W

Arm C: MM-398 80mg/m2 IV Q2W

Other Name: PEP02
Drug: 5 Fluorouracil

Arm B: 5 Fluorouracil 2000 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: 5 Fluorouracil 2400 mg/m2 IV every 2 weeks

Other Name: 5-FU
Drug: Leucovorin

Arm B: Leucovorin 200 mg/m2 IV for 4 weeks followed by 2 weeks of rest every 6 weeks

Arm C: Leucovorin 400 mg/m2 IV every 2 weeks

Other Name: Folinic Acid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the exocrine pancreas
  • Metastatic disease
  • Documented disease progression after prior gemcitabine based therapy
  • KPS >/= 70
  • Adequate bone marrow function
  • Adequate hepatic function
  • Adequate renal function

Exclusion Criteria:

  • Active CNS metastasis
  • Clinically significant GI disorders
  • Severe arterial thromboembolic events less than 6 months before inclusion
  • NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
  • Active infection or uncontrolled fever
  • Pregnant or breast feeding patients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01494506

  Show 79 Study Locations
Sponsors and Collaborators
Merrimack Pharmaceuticals
Investigators
Study Director: Eliel Bayever, MD Merrimack Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merrimack Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01494506     History of Changes
Other Study ID Numbers: MM-398-07-03-01 
Study First Received: December 14, 2011
Results First Received: November 25, 2015
Last Updated: February 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Merrimack Pharmaceuticals:
Pancreatic cancer
MM-398
PEP02
Metastatic pancreatic cancer
Gemcitabine refractory pancreatic cancer
Second line pancreatic cancer treatment
Pancreatic cancer post gemcitabine therapy

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Fluorouracil
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016