Single-agent Cobimetinib for Adults With Histiocytic Disorders

NCT02649972 | Completed Phase 2 Results

• 1 other identifier: 15-216
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out what effects, good or bad, Cobimetinib has in patients with histiocytosis. Cobimetinib is an investigational oral medication that blocks MEK1.

Conditions

Histiocytic Disorders

Keywords

Cobimetinib; 15-216

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  by PET Response Criterial (PRC), with a dichotomous BOR of CR or PR versus neither of those. Assuming we use this binary endpoint of response, defined as best overall response of CR or PR versus not using the PET Response Criteria (PRC), a sample size of 18 patients provides 90% power to test the hypothesis that the response rate is promising (defined as 35% or higher) against a non-promising rate of 10% or lower.

  1 year

Study Arms (1)

Cobimetinib

EXPERIMENTAL

This is an open-label, multicenter, phase II study exploring the efficacy and safety of single-agent Cobimetinib in patients with histiocytic disorders whose tumors are 1) BRAFV600 wildtype or 2) BRAFV600E mutant and are intolerant to, or unable to access, BRAF inhibitors. Visits during the treatment period are to be completed on Day 1, Day 15 (this visit can be by telephone), Day 29, and every 28 days thereafter. For patients treated on the study for six months, at the discretion of the Principal Investigator, visits can be spaced out to every 56 days (every 2 cycles instead of every cycle). After 24 cycles of treatment, if imaging demonstrates sustained stability in the opinion of the principal investigator, tumor assessments can be performed ever 1 year.

Drug: Cobimetinib

Interventions

Cobimetinib DRUG

Cobimetinib will be administered at a dose of 60mg daily for 21 days on, then 7 days off, in a 28 day treatment cycle. Patients will have the option to discontinue treatment after 12 cycles and will be monitored for disease relapse for an additional 12 months. In the event that disease relapse occurs within the 12 month monitoring period, patients will restart treatment and continue on study. Upon restarting, the assessment schedule will restart at rechallenge cycle 1(RC-1) and all assessments will occur at the frequency and intervals. Cycle 1 Day 15 visits will not be required for patients that restart treatment after relapse. Participants will re-sign consent upon rechallenging.

Cobimetinib

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed histiocytic disorder or histologic findings compatible with a histiocytic disorder in the context of confirmatory radiologic findings confirmed by the enrolling institution.
• One of the following:
• Documentation of BRAF V600E mutation and inability to access of BRAF inhibitor or prior treatment with a BRAF inhibitor discontinued due intolerable side effects or toxicity prior to progression, -OR-
• Documentation of wild-type BRAF V600 mutational status
• Patients with BRAF-mutated ECD/LCH who have had disease progression on BRAF inhibitor therapy would be eligible but would require tissue biopsy (or available tissue) for genotyping before participating.
• Measurable disease according to PET Response Criteria, confirmed by the MSK investigator radiologist, with the exception of patients with cutaneous disease that can be measured and followed by RECIST criteria
• Histiocytic disorder must be (a) multi-system disease or (b) disease that is recurrent or refractory to standard therapies, or (c) single-system disease with that is unlikely to benefit from conventional and less toxic therapies, based on the best available evidence (for example, CNS or cardiac infiltration, retroperitoneal fibrosis, prior chemotherapy, or other medical history or co-morbidities, etc)
• Life expectancy \> 12 weeks
• Age ≥ 16 years
• ECOG performance status ≤ 3 (May be converted from Karnofsky Performance Status)
• Adequate bone marrow function as indicated by the following:
• ANC \> 1000/uL
• Platelets ≥ 50,000/uL
• Hemoglobin ≥ 8.5 g/dL.
• Patients with cytopenias below these thresholds deemed to be the result of disease will be considered eligible.

You may not qualify if:

• Prior treatment with a MEK inhibitor
• Active infection requiring intravenous antibiotics
• Pregnant, lactating or breast feeding women
• Prior radiation therapy within the last 14 days
• Unwillingness or inability to comply with study and follow-up procedures.
• Any foods/supplements that are strong inhibitors or inducers of CYP3A are prohibited at least 7 days prior to initiation of and during study treatment
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, RVO, or neovascular macular degeneration
• Uncontrolled glaucoma with intra-ocular pressures \> 21mmHg
• Serum cholesterol ≥ Grade 2
• Hypertriglyceridemia ≥ Grade 2
• Hyperglycemia ≥ Grade 2
• History of clinically significant cardiac dysfunction, unless deemed to be the direct result of disease, including the following:
• Current unstable angina
• Symptomatic congestive heart failure of NYHA class 2 or higher
• Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 2 are eligible).

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

cobimetinib

Results Point of Contact

• Title: Dr. Eli Diamond, MD
• Organization: Memorial Sloan Kettering Cancer Center

diamone1@mskcc.org

212-610-0243

Study Officials

• Eli Diamond, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 8, 2016
• Study Start: January 1, 2016
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2022-12

Locations

US (2)