A Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers (Monotherapy)

• ClinicalTrials.gov Identifier: NCT00911898
• Recruitment Status: Completed
• First Posted: June 3, 2009
• Results First Posted: September 15, 2014
• Last Update Posted: January 13, 2015
• Sponsor: Merrimack Pharmaceuticals
• Information provided by (Responsible Party): Merrimack Pharmaceuticals

Study Description

Brief Summary:

This study is an open-label Phase 1 trial of MM-111.

Condition or disease	Intervention/treatment	Phase
Her2 Amplified Solid Tumors; Metastatic Breast Cancer	Drug: MM-111	Phase 1

Detailed Description:

Phase 1: Patients with any solid tumor type may be enrolled to evaluate the safety and tolerability of MM-111.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 and Pharmacologic Study of MM-111 in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Cancers
• Study Start Date: June 2009
• Actual Primary Completion Date: March 2012
• Actual Study Completion Date: March 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: MM-111	Drug: MM-111; For Phase 1: Dose-escalation cohorts, drug is administered weekly via IV

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) or Maximum Feasible Dose [ Time Frame: 28 days ]
   The Maximum Tolerated Dose (MTD) was defined as the highest dose level in which a DLT is experienced by fewer than two patients in a cohort of 3 - 6 patients. If a DLT is observed in at least two patients in a cohort of 3 - 6 patients, the MTD will be determined to have been exceeded and an additional three patients (up to a total of six) are to be treated at the next lower dose level.

Secondary Outcome Measures :

1. To Determine the Clinical Activity of MM-111 in Patients Based on Objective Response Rate (ORR), Duration of Response (DoR), Progression Free Survival (PFS), and 16 & 24-week Clinical Benefit Rate (CBR) [ Time Frame: December 2011 ]
2. To Explore the Role Functional Imagining (FDG-PET CT Scan), as a Predictor of Clinical Activity [ Time Frame: December 2011 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed advanced cancer that is:

  • HER2 amplified (IHC 2+ or greater) based on archived tumor evaluation
  • Heregulin positive based on a study required fresh biopsy sample performed at screening and confirmed by central laboratory
• Patients must have blocks of archived formalin-fixed, paraffin-embedded tumor tissue available for sectioning and immunohistochemical staining
• Patient's cancer must have recurred or progressed following standard therapy, have not responded to standard therapy, or for which no standard therapy exists.
• Patients must be >= 18 years of age
• Patients or their legal representatives must be able to understand and sign an informed consent
• Patients may have measurable or non-measurable tumor(s)
• Patients should have ECOG Performance Score (PS) 0 or 1

• Patients must have adequate bone marrow reserves as evidenced by:

  • Absolute neutrophil count (ANC) >= 1,500/uL and
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9 g/dL
• Patients must have tumor tissue amenable to biopsy
• Patients must be willing to undergo biopsy prior to treatment to MM-111

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 greater than 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 primary or metastatic CNS malignancies (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
• Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies (patients with a history of hypersensitivity to trastuzumab, a humanized antibody, are not excluded)
• Patients with known HIV, hepatitis B or C (if patients have previously been treated for C and have undetectable viral loads, they can be considered eligible for the trial)

Contacts and Locations

Locations

United States, California

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

United States, Indiana

Indiana University (IUPUI)

Indianapolis, Indiana, United States, 46268

United States, Pennsylvania

Fox Chase Center

Philadelphia, Pennsylvania, United States, 19111

United States, Texas

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Merrimack Pharmaceuticals

Investigators

• Principal Investigator: Muralidhar Beeram, MD; The START Center for Cancer Care

More Information

• Responsible Party: Merrimack Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00911898
• Other Study ID Numbers: MM-111-01-100
• First Posted: June 3, 2009
• Results First Posted: September 15, 2014
• Last Update Posted: January 13, 2015
• Last Verified: December 2014

Keywords provided by Merrimack Pharmaceuticals:

Her2 amplified solid tumors; Breast Cancer; Her3/ErbB3; Bispecific Antibody

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases