To evaluate the efficacy beyond progression of vemurafenib combined with cobimetinib associated with local treatment compared to second-line treatment in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib.

Phase 1

• Conditions: BRAFV600 mutation-positive metastatic melanoma in focal progression; MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003038-98-IT
• Lead Sponsor: INTERGRUPPO MELANOMA ITALIANO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 10 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

- Patients with histologically confirmed melanoma, either unresectable Stage IIIc or Stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition;
- Patients previously untreated for metastatic melanoma;
- Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) by a validated mutational test;
- Adequate performance status to receive vemurafenib and cobimetinib therapy as determined by treating physician.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

Cancer-related exclusion criteria:
1. Palliative radiotherapy within 7 days prior to the first dose of program treatment.
2. Patients with active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years except for patients with resected melanoma, resected BCC, resected cutaneous SCC, resected melanoma in situ, resected carcinoma in situ of the cervix, and resected carcinoma in situ of the breast.
Exclusion criteria based on organ function:
Ocular:
3. Evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment / central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration.
4. Systemic risk factor for RVO including uncontrolled glaucoma, uncontrolled hypercholesterolemia, hypertriglyceridemia or hyperglycemia.
Cardiac:
5. History of clinically significant cardiac dysfunction, including the following:
a) Current unstable angina.
b) Symptomatic congestive heart failure of New York Heart Association class 2 or higher.
c) History of congenital long QT syndrome or mean (average of triplicate measurements) QTcF = 450 msec at baseline; presence of clinically significant ventricular or atrial dysrhythmias = Grade 2.
d) Uncontrolled hypertension = Grade 2 (patients with a history hypertension controlled with anti-hypertensives to = Grade 1 are eligible).
e) Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower.
General exclusion criteria:
6. Current severe, uncontrolled systemic disease.
7. Major surgery or traumatic injury within 14 days prior to first dose of program treatment.
8. History of malabsorption or other condition that would interfere with absorption of program drugs.
9. Hypersensitivity to the active substance or to any of the excipients.
10. Pregnant or breastfeeding women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the efficacy, in terms of overall survival, of vemurafenib combined with cobimetinib associated with local treatment compared with second-line therapy in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib.;Secondary Objective: - To compare progression-free survival of patients receiving treatment beyond focal progression vs second-line treatment;<br>- To compare the adverse event profiles in patients receiving treatment beyond progression vs. second-line treatment;<br>- To evaluate the prognostic role of focal versus non-focal progressive disease.;Primary end point(s): The primary endpoint is Overall Survival (OS) for patients with focal progression.;Timepoint(s) of evaluation of this end point: From the day of randomization to the day of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression Free Survival (PFS) for patients with focal progression. ; OS for patients with non-focal progression.; Prognostic role in terms of OS of focal compared with non-focal progressive disease. ; Safety based on the following variables: Nature, frequency, severity, and timing of adverse events and serious adverse events; Changes in vital signs, physical findings and clinical laboratory results during and following vemurafenib + cobimetinib administration.;Timepoint(s) of evaluation of this end point: From the day of randomization to the day of disease progression or death from any cause.; During the study; During the study; During the study