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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-GB
Lead Sponsor
ovartis Pharma AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
600
Inclusion Criteria

1. =18 years of age
2. Signed informed consent must be obtained prior to participation in the study.
3. Completely resected histologically confirmed cutaneous melanoma
stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] see appendix 16.1] no more than 12 weeks, from last surgery, before Day 1
a. Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
b. Patients who have previously had Stage III melanoma at any time are
not eligible.
c. Recovered from definitive surgery (e.g. no uncontrolled wound
infections or indwelling drains).
d. Complete nodal resection is not mandatory for microscopic (SNB) disease
e. Full therapeutic lymph node dissection (TLND) is required for macroscopic disease, as per established treatment guidelines.
• V600E/K mutation positive using a validated local test
• 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
NameTimeMethod
Main Objective: To assess whether an adapted AE- management algorithm for pyrexia will reduce the incidence of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia compared to historical control;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>6) To evaluate overall safety;Primary end point(s): The composite rate of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated patients.;Timepoint(s) of evaluation of this end point: Base line up to 12 months
Secondary Outcome Measures
NameTimeMethod
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