Study of dabrafenib+trametinib in the Adjuvant treatment of stage III BRAF V600+ melanoma after complete resection to evaluate the impact on pyrexia related outcomes

Phase 1

Conditions: Stage III BRAF V600 mutation-positive melanoma
MedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-000168-27-IT

Lead Sponsor: OVARTIS PHARMA AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 552

Inclusion Criteria

• Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]
• V600E/K mutation positive using a validated local test
• Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
• Patients who have previously had Stage III melanoma at any time are not eligible
• Recovered from definitive surgery (e.g. no uncontrolled wound
infections or indwelling drains).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
Other protocol-defined inclusion criteria may apply
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 480
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

• Uveal or mucosal melanoma
•Evidence of metastatic disease including unresectable in-transit metastasis
•Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
•Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ
•History or current evidence of cardiovascular risk
•A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy
Other protocol-defined exclusion criteria may apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess whether an adapted AE- management algorithm for pyrexia will reduce the incidence of pyrexia related outcomes;Secondary Objective: The secondary objectives for this study are:<br>1) To evaluate relapse-free survival (RFS) at 12 and 24 months<br>2) To evaluate overall survival (OS) rate at 12 and 24 months<br>3) To evaluate pyrexia<br>4) To evaluate the overall adverse events (AE) rate leading to permanent treatment discontinuation by 12 months<br>5) To evaluate (Health-Related Quality Of<br>Life ) HRQOL measures assessed using FACT-M<br>;Primary end point(s): The composite rate of grade 3/4 pyrexia,<br>hospitalization due to pyrexia, or permanent<br>treatment discontinuation due to pyrexia by 12<br>months in overall treated subjects;Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): RFS rate at 12 and 24 months RFS is defined as the time from the first dose<br>of the study medication to disease recurrence<br>or death from any cause at 12 and 24 months<br>; OS is defined as the time from the first dose of<br>study medication to date of death due to any<br>cause at 12 and 24 months<br>; Frequency, number of episodes, duration, AE management (including<br>concomitant medications and study treatment modifications) due to<br>pyrexia; The proportion of patients in the study who permanently discontinued<br>treatment due to any Adverse event by 12 months; Changes in the HRQOL from baseline will be assessed using by FACTM questionnaire; Safety will be assessed by the frequency and severity of adverse events (AEs), serious AEs (SAEs) and laboratory abnormalities;Timepoint(s) of evaluation of this end point: 12 and 24 months; 12 and 24 months; 24 months; 12 months; 24 months; 24 months

Related Trials