Pembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer
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|ClinicalTrials.gov Identifier: NCT04675710|
Recruitment Status : Recruiting
First Posted : December 19, 2020
Last Update Posted : August 13, 2021
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Gland Anaplastic Carcinoma Thyroid Gland Squamous Cell Carcinoma||Procedure: Conventional Surgery Drug: Dabrafenib Radiation: Intensity-Modulated Radiation Therapy Biological: Pembrolizumab Other: Quality-of-Life Assessment Drug: Trametinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pembrolizumab in Combination With Dabrafenib and Trametinib as a Neoadjuvant Strategy Prior to Surgery in BRAF-Mutated Anaplastic Thyroid Cancer|
|Actual Study Start Date :||June 24, 2021|
|Estimated Primary Completion Date :||June 30, 2024|
|Estimated Study Completion Date :||June 30, 2024|
Experimental: Treatment (dabrafenib, trametinib, pembrolizumab)
Patients receive 21-day cycles of dabrafenib 150 mg orally (PO) twice daily from Days 1-21, trametinib 2mg PO once daily from Days 1-21, and pembrolizumab 200mg intravenously (IV) on Day 1 of each cycle.
Procedure: Conventional Surgery
Radiation: Intensity-Modulated Radiation Therapy
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Complete gross surgical resection (R0 or R1 resection) [ Time Frame: Up to 5 cycles (1 cycle = 21 days) ]Overall R0/R1 resection rate will be defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive (R1) surgical margins. We will test the hypothesis that the R0/R1 resection rate is greater than historical rate of 5%.
- Overall survival (OS) [ Time Frame: Up to 72 months ]OS will be measured as the time from the start of any trial treatment to death from any causes. Kaplan-Meier method will be used to estimate the median survival time across all patients and its 95% confidence intervals (CI).
- Tumor response [ Time Frame: Up to 42 months ]Objective tumor response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Progression free survival (PFS) [ Time Frame: Up to 42 months ]PFS will be measured as the time from the start of the treatment to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by RECIST version 1.1.
- Surgical morbidity/complexity [ Time Frame: Up to 5 cycles (1 cycle = 21 days) ]Surgical morbidity/complexity will be measured at enrollment, prior to surgery and at surgery. The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score are incorporated, specifying on a scale with 5 levels of complexity and morbidity of the surgery [mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)].
- Number of patients with adverse events as a measure of safety of neoadjuvant dabrafenib, trametinib, and pembrolizumab [ Time Frame: Up to 5 cycles (1 cycle = 21 days) ]Frequency and severity of adverse events as a measure of safety profile for neoadjuvant concurrent administration of dabrafenib, trametinib, and pembrolizumab (DTP) will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
- Number of patients with adverse events as a measure of safety of postoperative pembrolizumab plus IMRT [ Time Frame: Over the course of adjuvant IMRT plus 2 weeks of safety follow-up, assessed up to 2 months ]Frequency and severity of adverse events as a measure of safety profile for concurrent administration of postoperative pembrolizumab with IMRT will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
- Locoregional control [ Time Frame: Up to 42 months ]Locoregional control will be measured as the time from the start of any trial treatment to the first locoregional recurrence/progression event.
- Health related quality of life [ Time Frame: Up to 42 months ]Changes of health-related quality of life will be measured by the European Quality of Life 5 Dimension Questionnaire (EQ-5D). The EQ-5D consists of health state description and evaluation. The health state description consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), with each dimension specifying five levels of severity [best (1)-worst (5)]. The health state evaluation is assessed using the visual analogue scale ([worse (0)-best (100)].
- Patient-reported symptoms [ Time Frame: Up to 42 months ]Symptom burden experienced by patients will be measured by the M.D. Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) instrument.
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): NCT04675710
|Contact: Mark Zafereo||713-563-9683||MZafereo@mdanderson.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Mark Zafereo 713-563-9683 MZafereo@mdanderson.org|
|Principal Investigator: Mark Zafereo|
|Principal Investigator:||Mark Zafereo||M.D. Anderson Cancer Center|