Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

Browse trials for

• Melanoma 3,006
• Neoplasm Metastasis 3,517
• Brain Neoplasms 1,960

Keywords

• BRAF V600K mutation
• Metastatic Melanoma
• BRAF V600R mutation
• BRAF V600D mutation
• BRAF V600E mutation
• Brain metastases BRAF inhibitor
• Intracranial

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 127 is above the median of 38 across 2,351 interventional studies indexed under Melanoma.

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Study arms

• Experimental
  Cohort A

  Subjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity.

  Drug: Dabrafenib · Drug: Trametinib

• Experimental
  Cohort B

  Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

  Drug: Dabrafenib · Drug: Trametinib

• Experimental
  Cohort C

  Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

  Drug: Dabrafenib · Drug: Trametinib

• Experimental
  Cohort D

  Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

  Drug: Dabrafenib · Drug: Trametinib

Interventions

• DrugDabrafenib

  Dabrafenib will be provided as 50 mg and 75 mg capsules

• DrugTrametinib

  Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Primary outcomes

1. Intracranial Response (IR) Rate in Cohort A

   The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response.

   Time frame: From the start of treatment until disease progression or the start of new anti-cancer therapy

Secondary outcomes

1. Intracranial Response Rate of Cohorts B, C and D

   The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response. No hypothesis testing completed for cohort A, B,C and D

   Time frame: Approximately 2 years

2. Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort

   Disease Control rate is defined as the percentage of subjects achieving a confirmed intracranial/extracranial/overall CR or PR or SD or Non-CR/Non-PD. This is based on investigator-assessed response. No hypothesis testing completed for cohort A, B,C and D

   Time frame: Approximately 2 years

3. Extracranial Response Rate (ER) for Each Cohort

   Extracranial Response Rate was defined as the percentage of participants with Complete response (CR) or Partial response (PR) at anytime. This is based on investigator-assessed response. No hypothesis testing completed for cohort A,B,C and D

   Time frame: Approximately 2 years

4. Overall Response (OR) for Each Cohort

   the number of subjects with a confirmed overall Complete response (CR) or Partial response (PR) by investigator assessment using the Response evaluation criteria in solid tumors (RECIST 1.1 criteria). To determine the overall response, all target and non-target lesions will be assessed using modified RECIST 1.1 criteria.

   Time frame: Approximately 2 years

5. Duration of Intracranial, Extracranial and Overall Response for Each Cohort

   Duration of intracranial, extracranial and overall response, are defined as the time from first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression. No hypothesis testing completed for cohort A,B,C and D

   Time frame: From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression

6. Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment

   PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. No hypothesis testing completed for cohort A,B,C and D

   Time frame: From the first dose to the earliest date of disease progression or death

7. Overall Survival (OS) for Each Cohort

   Overall survival (OS) is defined as the time from the first dose until death due to any cause. No hypothesis testing completed for cohort A,B,C and D

   Time frame: From the first dose to death

Baseline characteristics

Publications

• Syeda MM, Wiggins JM, Corless BC, Long GV, Flaherty KT, Schadendorf D, Nathan PD, Robert C, Ribas A, Davies MA, Grob JJ, Gasal E, Squires M, Marker M, Garrett J, Brase JC, Polsky D. Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study. Lancet Oncol. 2021 Mar;22(3):370-380. doi: 10.1016/S1470-2045(20)30726-9. Epub 2021 Feb 12. PubMed 33587894 ↗
• Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. doi: 10.1016/S1470-2045(17)30429-1. Epub 2017 Jun 4. PubMed 28592387 ↗

Study documents

• Statistical analysis plan · Mar 5, 2018
• Study protocol · Jun 21, 2017

Documents are hosted by the registry — open the source record to download them.