Secured access to vemurafenib for patients with tumors harboring BRAF genomic alterations. - AcSé Vemurafenib

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2014-001225-33-FR
• Date of registration: 31/07/2014
• Prospective Registration: No
• Primary sponsor: UNICANCER
• Public title: Secured access to vemurafenib for patients with tumors harboring BRAF genomic alterations. - AcSé Vemurafenib
• Scientific title: Secured access to vemurafenib for patients with tumors harboring BRAF genomic alterations. - AcSé Vemurafenib
• Date of first enrolment: 21/07/2014
• Target sample size: 500
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001225-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France

Contacts

• Name: Head of Personalized Medicine
• Affiliation: UNICANCER

• Name: Head of Personalized Medicine
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female = 18 years of age
2. Unresectable locally advanced or metastatic histologically confirmed malignancy (excluding melanoma V600 mutation) resistant or refractory to standard therapy or for which standard or curative therapy does not exist or is not considered appropriate by the Investigator and are not eligible to an appropriate ongoing clinical trial. For Hairy Cell Leukemia: .patients must have relapsed and/or be refractory HCL candidate for treatment after 2 lines of purine analogues treatment.
. Serum bilirubin = 1.5 times ULN
. Alkaline phosphatase = 2.5 times ULN (= 5 times ULN if considered due to tumor)
* not applicable if biological abnormality(ies) is (are) fully related to the malignant disease itself.
3. Patient with BRAF V600 mutation determined on the primary and/or metastatic lesion in the following pathologies:
. NSCLC
. Ovarian cancer
. Cholangiocarcinoma
. Thyroid cancer
. Prostatic cancer
. Bladder cancer
. Sarcoma/GIST
. Multiple myeloma
. Chronic Lymphocytic Leukemia (CLL)
. Hairy cell leukaemia (HCL) (this excludes Hairy Cell Leukemia variant types, marginal zone splenic lymphoma (MZL), splenic red pulp lymphoma (SRPL) patients)
Or patient with same or any other pathology than those listed above who is harbouring another activating BRAF mutation or BRAF amplification on his tumor .
4. Measurable disease according to RECIST 1.1 guidelines for solid tumors with target lesion of at least 10 mm and presence of at least one RECIST-measurable lesion outside of a previously radiated field or potential palliative irradiation fields, International Myeloma Working group Response Criteria for myeloma, IWCLL Chronic Lymphocytic Leukemia and clinical/biological parameters for Hairy cell leukaemia (Serum M-protein > 0.5 g/dL; Urine M-protein > 200 mg per 24 hours; Involved FLC level > 10 mg/dL (> 100 mg/L) provided serum FLC ratio is abnormal).
5. Patients who had received any previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, i.e. = grade1, with a mandatory free interval of at least 3 weeks for systemic or radiotherapy treatments, and at least 5 half-lives for targeted drugs.
6. Patients who had received any investigational drug are eligible after a 4-week wash-out period or a wash-out period equivalent to 5 half-lifes of the product, depending on the longest period
7. Adequate hematologic*, renal* and liver function*, as defined by the following laboratory values; test performed within 7 days prior to the first dose of vemurafenib:
. Hemoglobin = 9 g/dL
. Absolute neutrophil count (ANC) = 1.5 x 10^9/L
. Platelet count = 100 x 10^9/L
. Serum creatinine = 1.5 times upper limit of normal (ULN) or creatine clearance (CrCl) > 50 mL/min by Cockroft–Gault formula (Protocol Appendix 1)
. Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) = 2.5 times ULN (= 5 times ULN if considered due to primary or metastatic liver involvement)
8. Normal values for calcium, magnesium and
Exclusion criteria:
1) . V600 BRAF mutated melanoma patients
2) Patient eligible to a clinical trial with an anticancer drug (including vemurafenib) targeting the same BRAF molecular alteration in the same type/localization as the patient’s cancer presentation open to accrual in FrancePatient not eligible in this trial are still eligible for the AcSé study.
3) Prior treatment with a BRAF or MEK inhibitor
4) Major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug
5) Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:
a) Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack. Ongoing congestive heart failure.
b) Pulmonary embolism within 30 days prior to first vemurafenib administration
c) Hypertension not adequately controlled by current medications within 30 days prior to first vemurafenib administration
d) Congenital long QT syndrome
e) Ongoing cardiac dysrhythmias of NCI CTCAE Grade = 2, uncontrolled atrial fibrillation of any grade, or machine-read ECG with QTc interval > 500 msec
f) Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function
g) Carcinomatous meningitis or leptomeningeal disease
h) Any uncontrolled infection
i) Other severe acute or chronic medical (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or end stage renal disease on hemodialysis or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for study entry
6) For MM, solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
7) Known hypersensitivity to vemurafenib or another BRAF inhibitor
8) Concurrent administration of any anti-cancer therapies (e.g., chemotherapy, other targeted therapy, experimental drug, etc.) other than those administered in this study
9) Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption.
10) Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
11) Individual deprived of liberty or placed under the authority of a tutor.
12) Unwillingness to practice effective birth control. Pregnant or lactating women.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patient with BRAF V600 mutation determined on the primary and/or metastatic lesion in the following pathologies: . NSCLC . Ovarian cancer . Cholangiocarcinoma . Thyroid cancer . Prostatic cancer . Bladder cancer . Sarcoma/GIST . Multiple myeloma . Chronic Lymphocytic Leukemia (CLL) . Hairy cell leukaemia (HCL) (this excludes Hairy Cell Leukemia variant types, marginal zone splenic lymphoma (MZL), splenic red pulp lymphoma (SRPL) patients)
MedDRA version: 17.0 Level: PT Classification code 10019053 Term: Hairy cell leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10039491 Term: Sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspe

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: ZELBORAF®
Product Code: RO5185426
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: VEMURAFENIB
CAS Number: 918504-65-1
Current Sponsor code: RO5185426-006
Other descriptive name: RG7204, PLX4032, Zelboraf
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Primary Outcome(s)

Main Objective: To explore the efficacy of vemurafenib as a single agent across diverse type of tumors guided by the presence of identified activating molecular alterations in the vemurafenib target gene, per cohort.

Timepoint(s) of evaluation of this end point: NA

Secondary Objective: To explore the efficacy of vemurafenib per pathology and per target
To assess the safety profile of vemurafenib
To explore whether molecularly driven, high quality multi-tumor screening phase II trials are feasible in the French multiinstitutional, multidisciplinary setting.

Primary end point(s): Objective response

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: NA

Secondary end point(s): Disease control rate
Response duration
Progression-free survival
Overall Survival
Safety (CTCAE v4.0)
Correlative research endpoints

Secondary ID(s)

UC-0105/1401

Source(s) of Monetary Support

Laboratoires ROCHE

Fondation ARC

Institut National du Cancer

Ethics review

Status: Approved
Approval date:
Contact: