A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04511013|
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : May 13, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acral Lentiginous Melanoma Clinical Stage IV Cutaneous Melanoma AJCC v8 Metastatic Cutaneous Melanoma Metastatic Malignant Neoplasm in the Brain Metastatic Melanoma Metastatic Mucosal Melanoma Pathologic Stage IV Cutaneous Melanoma AJCC v8||Drug: Binimetinib Drug: Encorafenib Biological: Ipilimumab Biological: Nivolumab||Phase 2|
I. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 between participants randomized to the triplet combination of encorafenib + binimetinib + nivolumab versus the doublet combination of ipilimumab + nivolumab among participants with BRAF-V600 mutant melanoma that has metastasized to the brain.
I. To estimate the overall survival (OS) of participants in each treatment arm. II. To estimate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial responses) per RECIST 1.1 in each treatment arm.
III. To estimate the intracranial response rate (ICRR), defined as confirmed and unconfirmed complete and partial response per modified RECIST for brain metastases (mRECIST).
IV. To evaluate the duration of response, per RECIST 1.1 and the duration of ICRR per mRECIST, and per Response Assessment in Neuro-Oncology (RANO)-Brain Metastases (BM) (and immunotherapy [i]RANO) in each treatment arm.
V. To evaluate the toxicity profile of each treatment arm. VI. To evaluate current and emerging radiographic response criteria (modified RECIST 1.1, modified RANO-BM and iRANO) by a retrospective blinded independent centralized review (BICR) of banked images.
I. To bank tumor tissue, cerebral spinal fluid (CSF), stool and blood samples for future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, binimetinib PO twice daily (BID) on days 1-28, and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 2 years, and then annually until 3 years after randomization.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||112 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase 2 Trial of Encorafenib + Binimetinib + Nivolumab vs Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases|
|Actual Study Start Date :||September 23, 2020|
|Estimated Primary Completion Date :||June 30, 2027|
|Estimated Study Completion Date :||June 30, 2027|
Experimental: Arm I (encorafenib, binimetinib, nivolumab)
Patients receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Experimental: Arm II (nivolumab, ipilimumab)
Patients receive nivolumab IV on day 1 of all cycles and ipilimumab IV over 30 minutes on day 1 of cycles 1-4. Cycles repeat every 21 days for 4 cycles and then every 28 days in the absence of disease progression or unacceptable toxicity.
- Progression-free survival [ Time Frame: From date of registration to date of first documentation of progression, or symptomatic deterioration, or death due to any cause, assessed up to 3 years after randomization ]Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Overall survival (OS) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 3 years after randomization ]Will be assessed by Immunotherapy Response Assessment Criteria for Intracranial Metastases (RANO-BM). Will construct Kaplan-Meier plots and estimate the median OS and construct 95% Brookmeyer-Crowley Confidence intervals.
- Intracranial response rate (ICRR) [ Time Frame: Up to 3 years after randomization ]The ICRR is defined as the best response when applying modified (m)RECIST criteria. Will compare intracranial response based on assessments per mRECIST, RANO-BM and immunotherapy (i)RANO criteria based on a review of the banked images. For each of these methods, the best response to treatment will be summarized by treatment arm, the percent agreement between each pair of methods will be reported along with a 95% confidence interval, and a p-value based on a two-sided McNemar's test will be calculated.
- Objective response rate [ Time Frame: Up to 3 years after randomization ]Will be assessed by RECIST 1.1.
- Duration of response [ Time Frame: Up to 3 years after randomization ]
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): NCT04511013
|Contact: Catrina Mireles||2106148808 ext email@example.com|
|Contact: Dana Sparks||12106148808 ext firstname.lastname@example.org|
|Principal Investigator:||Zeynep Eroglu||Southwest Oncology Group|