Disease or R Group HistiocytosesPhase 3COBRAHNCT04007848
Cobimetinib for BRAF-wild-type or Mutated Histiocytoses
A Phase 3 study testing Cobimetinib in people with Disease or R Group Histiocytoses, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disease or R Group Histiocytoses
- What is being tested?
- Cobimetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteFrance
- Study dates
- 25 Jul 2019to 14 Mar 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Médecine interne - La Pitié Salpêtrière
Paris, Paris, 75013
About this study
Official title: Cobimetinib for BRAF-wild-type or Mutated Histiocytoses : a Randomized, Placebo-controlled, Double Blind Study" COBRAH Study
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.
Read the detailed description
Histiocytoses are rare multisystemic disorders characterized by accumulation of histiocytes in various organs. Virtually all the patients have a somatic mutation in the RAS-RAF-MEK-ERK pathway. BRAF inhibitors are efficacious to treat BRAF-mutated patients but one third of the patients are BRAF-wild type. For these patients, preliminary data have shown an efficacy of the MEK inhibitor cobimetinib. This trial aims to evaluate the efficacy of cobimetinib for treating BRAF-wild type or mutated patients with L or R group histiocytoses.
The primary objective of the COBRAH trial is to demonstrate that the rate of objective metabolic response (complete or partial) according to PERCIST criteria is higher under Cobimetinib versus placebo.
The objective metabolic response according to PERCIST criteria (Haroche, et al. 2015) is defined by the Positron Emission Tomography (PET) response and will be used to evaluate the overall therapeutic response at month 3 (Week 12).
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 the patients as complete metabolic response, partial metabolic response (reduction of a minimum of 30% in target lesions), stable metabolic disease or progressive metabolic disease.
- Conditions
- Disease or R Group Histiocytoses
- Being tested
- Cobimetinib, Placebo oral tablet
- Medical subject headings
- Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CobimetinibDrug
Also called COTELLIC
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
Placebo oral tabletDrug
Also called PLACEBO
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
| Study group | Role | What they receive |
|---|---|---|
| Cobimetinib | Experimental | Experimental group : 36 histiocytoses's patients without or with BRAF V600E will be randomised in cobimetinib group Receives: Drug: Cobimetinib |
| Placebo | Placebo comparator | Control group : 18 histiocytoses's patients without or with BRAF V600E will be randomised in the placebo group Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at month 3
Secondary outcomes (5)
Overall survival
Overall survival is defined as the time between the date of randomisation and the death.
Measured: every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group
Progression-free survival
Progression-free survival is defined as the time between the date of randomisation and the first documented event of disease progression according to PERCIST criteria (Haroche, et al. 2015).
Measured: 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
All adverse events from clinical evaluations and laboratory measurements assessed by CTCAE v4.0
Measured: From the randomisation up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group.
Overall response of Cobimetinib (metabolic and tumor assessment)
Overall response of Cobimetinib (metabolic and tumor assessment) assessed after 36 weeks of Cobimetinib treatment or until Cobimetinib stop.
Measured: From the evaluation performed just before the treatment (Day 0 for Cobimetinib group, Week 12 for Placebo group)
CRP levels
CRP levels assessed from blood samples
Measured: At Baseline, Week 12, Week 24, Week 36 and Week 48 (for Placebo group)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start25 Jul 2019
- Primary completion5 Oct 2021
- Study completion14 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Disease or R Group HistiocytosesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fleur Dr COHEN AUBART, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04007848
- Sponsor's protocol ID
- P170932J - 2018-00222-23
- Acronym
- COBRAH
- Status last verified
- Dec 2024
- First submitted
- 18 Jun 2019
- Last updated
- 24 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cobimetinib for BRAF-wild-type or Mutated Histiocytoses : a Randomized, Placebo-controlled, Double Blind Study" COBRAH Study
- ClinicalTrials.gov ID
- NCT04007848
- Acronym / sponsor ID
- COBRAH / P170932J - 2018-00222-23
- Conditions
- Disease or R Group Histiocytoses
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 25 Jul 2019 (actual)
- Primary completion
- 5 Oct 2021 (actual)
- Study completion
- 14 Mar 2022 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Histiocytoses are rare multisystemic disorders characterized by accumulation of histiocytes in various organs. Virtually all the patients have a somatic mutation in the RAS-RAF-MEK-ERK pathway. BRAF inhibitors are efficacious to treat BRAF-mutated patients but one third of the patients are BRAF-wild type. For these patients, preliminary data have shown an efficacy of the MEK inhibitor cobimetinib. This trial aims to evaluate the efficacy of cobimetinib for treating BRAF-wild type or mutated patients with L or R group histiocytoses.
The primary objective of the COBRAH trial is to demonstrate that the rate of objective metabolic response (complete or partial) according to PERCIST criteria is higher under Cobimetinib versus placebo.
The objective metabolic response according to PERCIST criteria (Haroche, et al. 2015) is defined by the Positron Emission Tomography (PET) response and will be used to evaluate the overall therapeutic response at month 3 (Week 12).
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 the patients as complete metabolic response, partial metabolic response (reduction of a minimum of 30% in target lesions), stable metabolic disease or progressive metabolic disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cobimetinib | Experimental | Drug: CobimetinibExperimental group : 36 histiocytoses's patients without or with BRAF V600E will be randomised in cobimetinib group |
| Placebo | Placebo comparator | Drug: Placebo oral tabletControl group : 18 histiocytoses's patients without or with BRAF V600E will be randomised in the placebo group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CobimetinibAlso: COTELLICCobimetinib will be given at the dose of 40 milligrams once a day (21 days/28). Cobimetinib is available as 20 milligrams film-coated tablets | Drug | Cobimetinib |
| Placebo oral tabletAlso: PLACEBOPlacebo will be given at the dose of 40 milligrams once a day (21 days/28). Placebo is available as 20 milligrams film-coated tablets | Drug | Placebo |
Primary outcome
The objective metabolic responses
Time frame: at month 3
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.
5 secondary outcomes
Overall survival
Time frame: every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group
Progression-free survival
Time frame: 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
Time frame: From the randomisation up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group.
Overall response of Cobimetinib (metabolic and tumor assessment)
Time frame: From the evaluation performed just before the treatment (Day 0 for Cobimetinib group, Week 12 for Placebo group)
CRP levels
Time frame: At Baseline, Week 12, Week 24, Week 36 and Week 48 (for Placebo group)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fleur Dr COHEN AUBART principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cobimetinib in people with Disease or R Group Histiocytoses, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The objective metabolic responses (time frame: at month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2025.