Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib

Sponsor

Merrimack Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT02538627

Collaborator

(none)

Enrollment

Locations

Arms

14.2

Duration (Months)

Patient Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1 open-label, dose-escalation trial using "3+3" design, evaluating MM-151 co-administration with MM-121, MM-141, and trametinib at varying dose levels.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck	Drug: MM-151 Drug: MM-121 Drug: MM-141 Drug: trametinib	Phase 1

Detailed Description

This is a two-part Phase 1, non-randomized, open-label study of MM-151 plus MM-121, MM-141, or trametinib in patients with advanced, heregulin-positive lung, head and neck, and colorectal cancers. In part 1 of the study, cohorts of 3 or more patients will be treated at escalating doses of MM-151 in combination with MM-121, MM-141, and trametinib until a maximum tolerated combination dose for each combination is identified. In part 2 of the study, patients will be treated with the combination dose identified in part 1 of the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Multi Arm Study Evaluating the Safety, Pharmacology and Preliminary Activity of the Co-Administration of MM-151 With Seribantumab (MM-121), Istiratumab (MM-141), or Trametinib in Biomarker-selected Cancer Patients

Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Oct 5, 2016

Actual Study Completion Date :

Oct 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MM-151+MM-121 Dose Escalation MM-151 and MM-121 dose escalation in lung, head and neck, and colorectal cancers	Drug: MM-151 MM-151 Drug: MM-121 MM-121
Experimental: MM-151+ trametinib Dose Escalation MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.	Drug: MM-151 MM-151 Drug: trametinib trametininb Other Names: MEKINIST
Experimental: MM-151+MM-141 Dose Escalation MM-151 and MM-141 dose escalation in lung, head and neck, and colorectal cancers	Drug: MM-151 MM-151 Drug: MM-141 MM-141
Experimental: MM-151+trametinib Dose Escalation MM-151 and trametinib dose escalation in lung, head and neck, and colorectal cancers.	Drug: MM-151 MM-151 Drug: trametinib trametininb Other Names: MEKINIST
Experimental: Colorectal cancer Expansion Doses established in part 1 of the study	Drug: MM-151 MM-151 Drug: MM-121 MM-121 Drug: MM-141 MM-141 Drug: trametinib trametininb Other Names: MEKINIST
Experimental: Head and neck Expansion Doses established in part 1 of the study	Drug: MM-151 MM-151 Drug: MM-121 MM-121 Drug: MM-141 MM-141 Drug: trametinib trametininb Other Names: MEKINIST

Outcome Measures

Primary Outcome Measures

To find a phase II dose of MM-151 in combination with MM-121, MM-141, and trametinib based on maximum tolerated dose (MTD) in patients with lung, head and neck, and colorectal cancers [1.5 years]

Secondary Outcome Measures

Number of dose limiting toxicities (DLTs) within a group [1.5 years]
Adverse event profile of MM-151 in combination with MM-121, MM-141, and trametinib [1.5 years]
Objective response to MM-151 in combination with MM-121, MM-141, and trametinib based on RECIST [1.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must be >18 years of age
Patients must be able to provide informed consent
Willing 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 any study therapy). This applies to women of childbearing potential as well as fertile men and their partners
Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy, up to CTCAE grade 1
Patients must have either heregulin-positive cancer, cancer with RAS mutation, IGF-1 positive cancer, or RAS wild type cancer.

Exclusion Criteria:

Patients who are pregnant or lactating
Patients who have 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 (primary) or symptomatic CNS (primary or metastatic) malignancies; patients with CNS metastases who have undergone surgery or radiotherapy or who have been on a stable dose of corticosteroids for at least 2 weeks and whose disease is stable prior to the first scheduled day of dosing will be eligible for the trial.
Patients who have received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of the study treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado	Aurora	Colorado	United States	80045
2	Northside Hospital	Sandy Springs	Georgia	United States	30342
3	Northwestern	Chicago	Illinois	United States	60611
4	Washington University	Saint Louis	Missouri	United States	63110
5	Vanderbilt	Nashville	Tennessee	United States	37235