Dabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF V600 Mutation
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|ClinicalTrials.gov Identifier: NCT02231775|
Recruitment Status : Recruiting
First Posted : September 4, 2014
Last Update Posted : May 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|BRAF V600E Mutation Present BRAF V600K Mutation Present Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7||Drug: Dabrafenib Other: Laboratory Biomarker Analysis Procedure: Therapeutic Conventional Surgery Drug: Trametinib||Phase 2|
I. Study enrollment was stopped in April 2016 due to a substantial improvement in RFS in Arm B vs Arm A treated patients. The study was redesigned in August 2016 as a single-arm study with a new primary objective:
To compare relapse-free survival (RFS) between patients who develop a pathologic Complete Response (pCR) or do not achieve a pCR following dabrafenib and trametinib neoadjuvant combination therapy in patients with locally advanced BRAF V600 mutated melanoma.
I. To compare overall survival of patients with pathologic complete response (pCR) and patients without pCR who are receiving dabrafenib and trametinib neoadjuvant therapy followed by adjuvant combination therapy.
II. To identify biomarkers predictive of response through collection of serial blood draws and biopsies in patients receiving neoadjuvant dabrafenib and trametinib combination therapy.
III. To evaluate the safety of dabrafenib and trametinib in combination in this patient population.
I. To evaluate and perform further advanced imaging analysis on magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scanned (if available) images collected on patients enrolled onto this study.
Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 8 weeks. After completion of 8 weeks of dabrafenib and trametinib, patients undergo surgery. Approximately 1 week after surgery, patients receive dabrafenib PO BID and trametinib PO QD for 44 additional weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Neoadjuvant and Adjuvant Dabrafenib and Trametinib in Patients With Clinical Stage III Melanoma (Combi-Neo)|
|Actual Study Start Date :||October 22, 2014|
|Estimated Primary Completion Date :||October 31, 2019|
|Estimated Study Completion Date :||October 31, 2019|
Experimental: Treatment (dabrafenib, trametinib, surgery)
Patients receive dabrafenib PO BID and trametinib PO QD for 8 weeks. After completion of 8 weeks of dabrafenib and trametinib, patients undergo surgery. Approximately 1 week after surgery, patients receive dabrafenib PO BID and trametinib PO QD for 44 additional weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Procedure: Therapeutic Conventional Surgery
- Relapse-free survival (RFS) [ Time Frame: Up to 12 months ]RFS will be compared between patients with a pathologic complete response (pCR) and patients without a pCR using a two-sided log-rank test.
- Overall survival (OS) [ Time Frame: Up to 1 year ]The association between RFS and OS and covariates of interest will be assessed using Cox proportional hazards regression analysis.
- Complete pathologic response [ Time Frame: Up to 1 year ]Logistic regression will be used to assess the association between the probability of complete pathologic response and clinical and disease covariates of interest.
- Incidence of adverse events [ Time Frame: Up to 1 year ]Safety parameters will be tabulated by using Fisher's exact tests for categorical variables and Wilcoxon rank-sum tests for continuous variables.
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): NCT02231775
|Contact: Jennifer Wargoemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Jennifer Wargo 713-745-1553|
|Principal Investigator: Jennifer Wargo|
|Principal Investigator:||Jennifer Wargo||M.D. Anderson Cancer Center|