Evaluate the safety and the efficacy of Vemurafenib/PEG-interferon in melanoma patients

Phase 1

• Conditions: Evaluate the safety and the efficacy of Vemurafenib/PEG-interferon combination and the IFNAR1 upregulation lead by this treatment in advanced melanoma patients harboring the V600BRAF mutation; MedDRA version: 14.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003730-33-IT
• Lead Sponsor: Fondazione Melanoma ONLUS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-10-23
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

a)Patients over 18
b)Untreated and pretreated (no more than 1 treatment) patients with metastatic melanoma at stage unreseactable IIIb-IV, histologically confirmed, that show V600 type BRAF mutations. Patients eligible for Phase I may have been pretreated with the investigational study treatments.
c)Patient with measurable disease by RECIST v 1.1
d)Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 – 1
e)Patients who have successfully completed all the secondary side effects to previous systemic therapy
f)Patients with an appropriate hematologic, hepatic and renal functionality, assessed in the 7 days preceding the start of therapy, as well as:
•Absolute neutrophil count (ANC)> 1.5 X 109 / L
•Absolute platelet count > 100 X 109 / L
•Hemoglobin > 9 g/dl
•Serum creatinine < 1.5 times the normal maximum values or Creatinine Clearance > 50 mL/hr (Cockroft-Gault formula)
•Transaminase level (AST and ALT) < 2.5 times the normal maximum values
•Serum bilirubin < 1.5 times the normal maximum values
g)Negative pregnancy test performed within 7 days before beginning therapy (premenopausal women)
h)Patients of childbearing age (or with partners of childbearing age) must use effective contraception during therapy and for at least 6 months after the effective treatment
i)Absence of any psychological, familiar or social condition that may affect compliance with study protocol and scheduled follow-up
j)Dated and signed informed consent before any study procedure
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 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

a)Presence of symptomatic brain metastases
b)Previous malignant cancer during the 2 years preceding the signing of informed consent
c)Investigational study treatment within 28 days or 5 half-lives, whichever is longer, preceding the first dose of study treatments in this study
d)Pregnancy and/or breast feeding;
e)Nausea and vomit refractory to therapy, malabsorption, external biliary shunt, previous bowel resection, which could impair an adequate absorption
f)Any of these conditions occurring in the 6 months before the start of Vemurafenib therapy: heart attack, unstable angina and/or severe degree, congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, arterial hypertension not adequately controlled
g)History of atrial or ventricular arrhythmia, symptomatic> grade 2 (NCI CTCAE)
h)Hystory of retinopathy
i)Correct QT interval > 450msec to baseline history of congenital long QT syndrome
j)Uncontrolled medical condition among which endocrine disorders (such as hypothyroidism, hyperthyroidism and diabetes mellitus)
k)Other severe medical or psychiatric conditions or abnormalities of laboratory tests that may increase the risk associated with study participation or the assumption of Vemurafenib, or that may interfere with the interpretation of study results, which in the judgment of the Investigator can make the patient not eligible for the study
l)Unwillingness to practice adequate contraception
m)Prior systemic treatment with BRAFi or MEKi, or interferon alpha

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Phase I: Vemurafenib/PEG-interferon combination safety (MTD)<br>Phase II: 1) Vemurafenib/PEG-interferon combination efficacy (DRR); 2) IFNAR1 expression<br>;Secondary Objective: 1) Vemurafenib/PEG-interferon combination feasibility <br>2) Vemurafenib/PEG-interferon combination safety/toxicity <br>3) Correlation of possible markers with the outcome to the treatment<br>;Timepoint(s) of evaluation of this end point: Phase I: maximum 24 weeks<br>;Primary end point(s): Phase I: Adverse events (AEs) evaluated during the treatment period of Phase I (maximum 24 weeks).<br>Phase II: Evaluation of the activity of the treatment in terms of proportion of patients with durable response rate (DRR) lasting > 32 weeks; 2) Evaluation of the IFNR up-regulation in terms of the receptor expression in tumor biopsies.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Incidence of G3-4 toxicities (any type) <br>• To evaluate disease control rate (proportion with best response of CR+PR+SD) <br>• To evaluate time to response <br>•To evaluate time to progression of BM (Including incidence of BM in pts free from BMs at the time of enrolment) <br>•Overall survival (OS) <br>;Timepoint(s) of evaluation of this end point: from date of randomization until the date of first documented progression or date of Death for any cause whichever come first assessed up to week 32