Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

A Phase 1 and Pharmacologic Study of MM-151 in Patients With Refractory Advanced Solid Tumors

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design, evaluating MM-151 at varying dose levels and frequencies, and subsequently in combination with irinotecan.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Non Small Cell Lung Cancer; Advanced Solid Tumors; Triple Negative Breast Cancer; Squamous Cell Head and Neck Cancer
• Intervention / Treatment: Drug: MM-151; Drug: MM-151 + irinotecan

Detailed Description

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design exploring weekly, bi-weekly, and tri-weekly dosing schedules. Successive MM-151 monotherapy cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified, and subsequently in combination with irinotecan. The study consists of three parts as follows: MM-151 monotherapy dose escalation (Part 1); MM-151 monotherapy expansion cohort in cetuximab-refractory colorectal cancer (Part 2); MM-151 + irinotecan dose escalation (Part 3). It is expected that approximately 4 study sites will participate.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC (START)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
• Patients must be > 18 years of age
• Patients of their legal representatives must be able to understand and sign an informed consent form
• Patients must have evaluable or measurable tumor(s)
• Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy
• Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-151 (an effective form of contraception is an oral contraceptive or a double barrier method)

Exclusion Criteria:

• Patients for whom potentially curative antineoplastic therapy is available
• Patients who are pregnant or lactating
• Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.)
• Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MM-151 Dose Escalation; MM-151 Dose escalation frequency - once weekly, once every two weeks, once every three weeks	Drug: MM-151; MM-151
EXPERIMENTAL: MM-151 Expansion in KRAS wild type colorectal cancer; MM-151 given weekly	Drug: MM-151; MM-151
EXPERIMENTAL: MM-151 + irinotecan; MM-151 given weekly, irinotecan 180 mg/m2 given once every two weeks	Drug: MM-151 + irinotecan; MM-151 + irinotecan; Other Names: camptosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase II dose of MM-151 alone and in combination with irinotecan based either on the maximum tolerated dose (MTD) or maximum dose of 18 mg/kg in patients with advanced solid malignancies.	Two years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of dose limiting toxicities (DLTs) within a cohort	2 years
Adverse event profile of MM-151 alone and in combination with irinotecan	2 years
Objective response to MM-151 alone and in combination with irinotecan based on RECIST	2 years

Collaborators and Investigators

• Sponsor: Merrimack Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 24, 2012
• First Posted (ESTIMATE): January 30, 2012

Study Record Updates

• Last Update Posted (ACTUAL): March 21, 2018
• Last Update Submitted That Met QC Criteria: March 20, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: cancer; oncology; EGFR; Phase I; solid tumors; irinotecan; EGF receptor (ErbB1)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Antibodies, Monoclonal
• Other Study ID Numbers: MM-151-01-01-01