Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer
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|ClinicalTrials.gov Identifier: NCT03975231|
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : July 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|BRAF NP_004324.2:p.V600E BRAF V600K Mutation Present Thyroid Gland Anaplastic Carcinoma||Drug: Dabrafenib Radiation: Intensity-Modulated Radiation Therapy Drug: Trametinib||Phase 1|
I. To assess the safety and tolerability (maximum tolerated dose [MTD]) of concurrent intensity modulated radiation therapy (IMRT) and BRAF-MEK inhibitors dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer.
I. To assess overall objective response rate, time to progression of local recurrence, progression free survival and overall survival.
II. To assess pharmacokinetics during concurrent IMRT and dabrafenib plus trametinib therapy.
III. To assess pharmacodynamics of dabrafenib plus trametinib induction therapy.
IV. To assess mechanism of resistance to dabrafenib plus trametinib and radiation therapy.
OUTLINE: This is a dose-escalation study of dabrafenib.
INDUCTION: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 7-28 days in the absence of disease progression and unacceptable toxicity.
OPTIONAL SURGERY: Patients with resectable disease may undergo surgery 3 days after stop treatment of dabrafenib/trametinib, and move to Concurrent Radiation 14 days after surgery provided that surgical wound has healed. All other patients continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity.
CONCURRENT RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD at weeks 6-7. Within 2.5 hours of morning doses of dabrafenib/trametinib administration, patients undergo intensity modulated radiation therapy (IMRT) on Monday-Friday delivered over 6.5 weeks in the absence of disease progression or unacceptable toxicity.
POST-RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD for 4 weeks in the absence of disease progression and unacceptable toxicity.
MAINTENANCE: Patients with residual disease receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity. Patients stop dabrafenib and trametinib 8 weeks after achieving complete response. Patients with no residual disease stop dabrafenib and trametinib, with the option of restarting dabrafenib and trametinib at time of disease recurrence.
After completion of study treatment, patients are followed up every 2 months for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Concurrent Intensity Modulated Radiation Therapy (IMRT) and Dabrafenib/Trametinib in BRAF Mutated Anaplastic Thyroid Cancer|
|Actual Study Start Date :||May 4, 2020|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (dabrafenib, trametinib, IMRT)
See Detailed Description
Radiation: Intensity-Modulated Radiation Therapy
- Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT) [ Time Frame: 1 year ]
- Objective response rate [ Time Frame: 1 year ]Will be defined as the proportion of patients who have a partial response (PR), or complete response (CR) within the first 4 weeks of IMRT. Complete response (CR) and partial response (PR) will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be calculated with the exact binomial 95% confidence intervals.
- Time to progression for local disease recurrence [ Time Frame: 1 year ]Will be evaluated by RECIST criteria for disease limited to the radiation field (neck) following the first set of scans after completion of IMRT. Estimated by Kaplan-Meier method.
- Overall survival [ Time Frame: From the start date of the treatment to the date of death, assessed up to 1 year ]Estimated by Kaplan-Meier method.
- Progression free survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ]Estimated by Kaplan-Meier method.
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): NCT03975231
|Contact: The Ohio State University Comprehensive Cancer Center||1-800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Manisha H. Shah, MD 614-366-6994 firstname.lastname@example.org|
|Principal Investigator: Manisha H. Shah, MD|
|Principal Investigator:||Manisha H Shah, MD||Ohio State University Comprehensive Cancer Center|