Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations

NCT02304809 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UC-0105/14012014 001225 33
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with metastatic or unresectable locally advanced malignancies harboring BRAF genomic alterations, the biological target of vemurafenib, and who are no more amenable to curative treatment. 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.

Conditions

Solid Tumors; Hematologic Cancers; Metastatic Cancers

Keywords

metastatic or unresectable locally advanced malignancies.; genomic alterations; biological vemurafenib targets BRAF; genomic.

Outcome Measures

Primary Outcomes (1)

• The objective response rate (ORR) will be defined as the proportion of patients with a complete response (CR) or a partial response (PR) as best overall response during the study

  RECIST for solid tumors, International Myeloma Working Group Response Criteria for myeloma, IWCLL for CLL, clinical exam, blood tests (blood count) and bone marrow exam for Hairy Cell Leukemia.

  Determined after 8 weeks (2 cycles) of treatment

Secondary Outcomes (1)

• Safety profile of Vemurafenib (frequency of adverse events coded using the common toxicity criteria (CTC-V4.0) grade)

  Determined after 8 weeks (2 cycles) of treatment

Study Arms (1)

VEMURAFENIB

EXPERIMENTAL

all eligible patients entering the study will receive oral Vemurafenib as monotherapy. Vemurafenib ZELBORAF 240 mg tablets Per OS 960 mg twice daily, to a total daily dose of 1,920 mg Cycles are defined in 28-day periods Disease response will be assessed every 8 weeks Safety will be assessed continuously Treatment will be pursed until disease progression, unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient refusal.

Drug: Vemurafenib

Interventions

Vemurafenib DRUG

Vemurafenib is a low molecular weight, orally available, inhibitor of BRAF serine-threonine kinase. Mutations in the BRAF gene which substitute the valine at amino acid position 600 result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation

Also known as: Zelboraf

VEMURAFENIB

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female ≥ 8 years of age
• Unresectable locally advanced or metastatic histologically confirmed malignancy (excluding melanoma V600 mutation) resistant or refractory to standard therapy or for which standard 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.
• Patient with BRAF V600 mutation determined by the INCa platforms 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 the same or another pre-listed pathology harboring any type of activating BRAF alteration determined from outside the INCa platforms network.
• 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).

You may not qualify if:

• V600 BRAF mutated melanoma patients or colorectal cancer patients
• 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 France. Patient not eligible in this trial are still eligible for the AcSé study.
• Prior treatment with a BRAF or MEK inhibitor
• Major surgery or tumor embolization within 4 weeks and minor surgery within 2 weeks prior to the initiation of the study drug
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to:
• 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.
• Pulmonary embolism within 30 days prior to first vemurafenib administration
• Hypertension not adequately controlled by current medications within 30 days prior to first vemurafenib administration
• Congenital long QT syndrome
• Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, uncontrolled atrial fibrillation of any grade, or machine-read ECG with QTc interval \>460 msec
• Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function
• Carcinomatous meningitis or leptomeningeal disease
• Any uncontrolled infection
• 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
• For MM, solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• Fondation ARC: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (1)

Tredaniel

Paris, 75014, France

Location

Related Publications (1)

• Mazieres J, Cropet C, Montane L, Barlesi F, Souquet PJ, Quantin X, Dubos-Arvis C, Otto J, Favier L, Avrillon V, Cadranel J, Moro-Sibilot D, Monnet I, Westeel V, Le Treut J, Brain E, Tredaniel J, Jaffro M, Collot S, Ferretti GR, Tiffon C, Mahier-Ait Oukhatar C, Blay JY. Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations. Ann Oncol. 2020 Feb;31(2):289-294. doi: 10.1016/j.annonc.2019.10.022. Epub 2020 Jan 3.

  PMID: 31959346 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

Vemurafenib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jean-Yves PI Blay, MD

  CCLC LEON BERARD LYON

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2014
• First Posted: December 2, 2014
• Study Start: October 13, 2014
• Primary Completion: May 7, 2019
• Study Completion (Estimated): October 13, 2027
• Last Updated: August 1, 2025

Record last verified: 2025-06

Locations

FR (1)