Phase 2 Study Assessing Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations (AcSé)
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|ClinicalTrials.gov Identifier: NCT02304809|
Recruitment Status : Recruiting
First Posted : December 2, 2014
Last Update Posted : February 17, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumors Hematologic Cancers Metastatic Cancers||Drug: Vemurafenib||Phase 2|
This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent vemurafenib as a monotherapy in cohorts of patients with identified activating molecular alterations in BRAF gene. A cohort is defined by a pathology and a BRAF- alteration (eg ovarian cancer with BRAF V600 mutation).
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.
To investigate the additional molecular mechanisms in patients with tumor response versus patients without tumor response within the same cohort.
The study will include 11 cohorts of adult patients with the following cancers and alterations:
- NSCLC V600 mutated
- Ovarian cancer V600 mutated
- Cholangiocarcinoma V600 mutated
- Thyroid cancer V600 mutated
- Prostatic cancer V600 mutated
- Bladder cancer V600 mutated
- Sarcoma/GIST V600 mutated
- Multiple myeloma V600 mutated
- Chronic Lymphocytic Leukemia (CLL) V600 mutated
- Hairy cell leukaemia (HCL) V600 mutated (this excludes Hairy Cell Leukemia variant types, marginal zone splenic lymphoma (MZL), splenic red pulp lymphoma (SRPL) patients)
- Other pathology / other alteration than those pre-defined above.
The cohort named "Other" will include adult patients with tumor harboring BRAF genomic alterations only tested via emerging biomarkers programs or molecular pangenomic programs:
- with any other non-predefined pathology harboring a V600 mutation
- Same or other non-predefined pathology harboring non V600 activating mutations
- Same or other non-predefined pathology harboring BRAF amplifications.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Secured Access to Vemurafenib for Patients With Tumors Harboring BRAF Genomic Alterations|
|Study Start Date :||July 2014|
|Estimated Primary Completion Date :||February 2016|
|Estimated Study Completion Date :||February 2022|
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.
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
Other Name: Zelboraf
- 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 [ Time Frame: Determined after 8 weeks (2 cycles) of treatment ]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.
- Safety profile of Vemurafenib (frequency of adverse events coded using the common toxicity criteria (CTC-V4.0) grade) [ Time Frame: Determined after 8 weeks (2 cycles) of treatment ]The assessment of safety will be based mainly on the frequency of adverse events coded using the common toxicity criteria (CTC-V4.0) grade.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304809
|Contact: Céline Mahier||+ 33 1 44 23 55 email@example.com|
|Contact: Marta Jimenez||+ 33 firstname.lastname@example.org|
|Paris, France, 75014|
|Contact: JEAN TREDANIEL, MD 33 1 44 12 78 05 email@example.com|
|Principal Investigator:||Jean-Yves PI Blay, MD||CCLC LEON BERARD LYON|