Clinical trial NCT02538627: Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Colorectal Cancer
Non-small Cell Lung Cancer
Squamous Cell Carcinoma of the Head and Neck
Keywords: Heregulin-positive
EGFR
ErbB3
Phase I
Oncology
Cancer
IGF-1
MEKinhibitor
IGF-1R inhibitor
KRAS
NRAS
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-09-02
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 1.5 years
Secondary outcomes:
measure: Number of dose limiting toxicities (DLTs) within a group
timeFrame: 1.5 years
measure: Adverse event profile of MM-151 in combination with MM-121, MM-141, and trametinib
timeFrame: 1.5 years
measure: Objective response to MM-151 in combination with MM-121, MM-141, and trametinib based on RECIST
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Sandy Springs
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
Study officials:
References: