Cobimetinib for BRAF-wild-type or Mutated Histiocytoses

NCT04007848 | Completed Phase 3 DMC

• 1 other identifier: P170932J - 2018-00222-23
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

COBRAH is a randomized double-blind 2-steps controlled superiority trial, with 2 parallel groups. Patients will be randomly assigned in a 2:1 ratio to receive Cobimetinib orally or placebo during the first 12-weeks step, allowing the determination of the primary criteria.

Conditions

Disease or R Group Histiocytoses

Outcome Measures

Primary Outcomes (1)

• The objective metabolic responses

  The objective metabolic responses is the percentage of patients with a complete metabolic response, partial metabolic response (reduction of a minimum of 30% in target lesions), stable metabolic disease or progressive metabolic disease according to PERCIST criteria (Haroche, et al. 2015) at Month 3. PERCIST criteria is defined by the PET response and will be used to evaluate the overall therapeutic response at month 3. For PERCIST criteria, a quantitative analysis of uptake will be performed using the standard uptake value (SUV). Fitting regions of interest covering pathologic uptake will be used to define target lesions. PERCIST will be used to classify patients metabolic response.

  at month 3

Secondary Outcomes (5)

• Overall survival

  every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group

• Progression-free survival

  every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group

• Number of participants with adverse events as assessed by CTCAE v4.0

  From the randomisation up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group.

• Overall response of Cobimetinib (metabolic and tumor assessment)

  From the evaluation performed just before the treatment (Day 0 for Cobimetinib group, Week 12 for Placebo group)

• CRP levels

  At Baseline, Week 12, Week 24, Week 36 and Week 48 (for Placebo group)

Study Arms (2)

Cobimetinib

EXPERIMENTAL

Experimental group : 36 histiocytoses's patients without or with BRAF V600E will be randomised in cobimetinib group

Drug: Cobimetinib

Placebo

PLACEBO COMPARATOR

Control group : 18 histiocytoses's patients without or with BRAF V600E will be randomised in the placebo group

Drug: Placebo oral tablet

Interventions

Cobimetinib DRUG

Cobimetinib will be given at the dose of 40 milligrams once a day (21 days/28). Cobimetinib is available as 20 milligrams film-coated tablets

Also known as: COTELLIC

Cobimetinib

Placebo oral tablet DRUG

Placebo will be given at the dose of 40 milligrams once a day (21 days/28). Placebo is available as 20 milligrams film-coated tablets

Also known as: PLACEBO

Placebo

Eligibility Criteria

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

You may qualify if:

• Eligible patients should be at least 18 years of age,
• Have a histologically confirmed L or R group histiocytoses without BRAFV600E mutation detected with the use of a real-time polymerase chain reaction or with BRAFV600E mutation AND a contra-indication to BRAF inhibitors
• Have a measurable disease according to the PERCIST criteria with presence of at least one severe organ involvement (heart, vascular, central nervous system) OR a multisystemic disease with ≥3 organ involvement AND failure of a first-line treatment or contra-indication to these treatments,
• Accepting effective contraception during treatment duration (men and women childbearing potential) and 3 months after.
• Signed informed consent

You may not qualify if:

• Patients with severe hepatic, renal and cardiac outcomes
• Patients with myopathies at baseline
• Patients with retinal detachment at baseline
• Patients with inherited disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
• Patients with high bleeding risk.
• Allergies to iodized contrast media
• Simultaneous participation in another medical research
• Pregnancy or breast-feeding.
• No affiliation to the French Health Care System "sécurité sociale" OR no affiliation of European Health within the scope of Regulations (EEC) n° 1408/71 and 574/72 coordinating social security systems.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Médecine interne - La Pitié Salpêtrière

Paris, Paris, 75013, France

Location

Related Publications (1)

• Jouenne F, Benattia A, Tazi A. Mitogen-activating protein kinase pathway alterations in Langerhans cell histiocytosis. Curr Opin Oncol. 2021 Mar 1;33(2):101-109. doi: 10.1097/CCO.0000000000000707.

  PMID: 33315630 DERIVED

MeSH Terms

Conditions

Disease

Interventions

cobimetinib

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fleur Dr COHEN AUBART

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: July 5, 2019
• Study Start: July 25, 2019
• Primary Completion: October 5, 2021
• Study Completion: March 14, 2022
• Last Updated: January 24, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)