Disease or R Group Histiocytoses Clinical Trial
— COBRAHOfficial title:
Cobimetinib for BRAF-wild-type or Mutated Histiocytoses : a Randomized, Placebo-controlled, Double Blind Study" COBRAH Study
| Verified date | August 2023 |
| Source | Assistance Publique - Hôpitaux de Paris |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 54 |
| Est. completion date | March 14, 2022 |
| Est. primary completion date | October 5, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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. |
| Country | Name | City | State |
|---|---|---|---|
| France | Service de Médecine interne - La Pitié Salpêtrière | Paris |
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Overall survival | Overall survival is defined as the time between the date of randomisation and the death. | every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group | |
| Secondary | 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). | every 12 weeks up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group | |
| Secondary | 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 | From the randomisation up to 36 weeks for Cobimetinib group and 48 weeks for Placebo group. | |
| Secondary | 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. | From the evaluation performed just before the treatment (Day 0 for Cobimetinib group, Week 12 for Placebo group) | |
| Secondary | CRP levels | CRP levels assessed from blood samples | At Baseline, Week 12, Week 24, Week 36 and Week 48 (for Placebo group) |