Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer

NCT03975231 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 21308NCI-2019-02745R01CA246553OSU-17277
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

This trial studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) work together in treating patients with BRAF mutated anaplastic thyroid cancer. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving dabrafenib, trametinib, and IMRT together may kill more tumor cells.

Conditions

BRAF NP_004324.2:p.V600E; BRAF V600K Mutation Present; Thyroid Gland Anaplastic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of combination therapy of dabrafenib and trametinib administered concurrently with intensity-modulated radiation therapy (IMRT)

  1 year

Secondary Outcomes (4)

• Objective response rate

  1 year

• Time to progression for local disease recurrence

  1 year

• Overall survival

  From the start date of the treatment to the date of death, assessed up to 1 year

• Progression free survival

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Study Arms (1)

Treatment (dabrafenib, trametinib, IMRT)

EXPERIMENTAL

See Detailed Description

Drug: Dabrafenib; Radiation: Intensity-Modulated Radiation Therapy; Drug: Trametinib

Interventions

Dabrafenib DRUG

Given PO

Also known as: BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436

Treatment (dabrafenib, trametinib, IMRT)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (dabrafenib, trametinib, IMRT)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

Treatment (dabrafenib, trametinib, IMRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic (histologic or cytologic) diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be ?consistent with anaplastic thyroid cancer? with the presence of a thyroid mass is acceptable; pathology showing additional types of thyroid cancer is allowed)
• Note: Tissue collection for central review is mandatory, but central review is not required for eligibility. Due to the aggressiveness of this disease, treatment will be started prior to central review.
• Presence of BRAF mutation (V600E or V600K) in tumor tissue.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2.
• Absolute neutrophil count \> 1,000/mcL.
• Hemoglobin \>= 9.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dl is acceptable).
• Platelets \> 75,000/mcL.
• Total bilirubin \< 1.5 x institutional upper limit of normal (unless due to Gilbert?s disease).
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x institutional upper limit of normal.
• Serum creatinine \< 1.5 x institutional upper limit of normal.
• Female patients of childbearing potential are required to have a negative serum pregnancy test within 14 days prior to the first dose of study medication.
• Females are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and for 4 months after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to study enrollment, for the duration of study participation, and for 16 weeks after completion of the last dose of study drug.
• Specific contraception requirements for females: Female subjects of childbearing potential must not become pregnant and are required to be sexually inactive by abstinence or use contraceptive methods with a failure rate of \< 1%. Sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception. Contraceptive methods with a failure rate of \< 1% include the following:
• Intrauterine device (IUD) or intrauterine system (IUS) that meets the \< 1% failure rate as stated in the product label,
• Male partner sterilization (vasectomy with documentation of Azoospermia) prior to the female subject's entry into the study, and this male is patient?s sole sexual partner. For this definition, ?documented? refers to the outcome of the investigator's/qualified physician designee?s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject?s medical records.

You may not qualify if:

• Patients with resectable stage IVA anaplastic thyroid cancer who are candidates for surgery and wish to proceed with surgery.
• Patients who have had external beam radiotherapy to neck or chest for cancer that would result in overlap of radiation therapy fields.
• Patients who have had cytotoxic chemotherapy, stereotactic brain radiation or external beam radiation within 2 weeks prior to study treatment initiation.
• Patients who have had oral multikinase inhibitors within 1 week prior to study treatment initiation.
• Patients that have not recovered from adverse events related to prior therapy for cancer to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 grade 2 or less except for alopecia.
• Patients previously treated with potent BRAF inhibitor or MEK inhibitor. Previous treatment with sorafenib is permitted.
• Patients that are receiving any other investigational agent.
• Patients that are currently taking any prohibitive medication.
• Patients with a history of other active malignancy requiring cancer treatment.
• Patients with uncontrolled brain metastases. Patients who are on a stable dose of corticosteroids for more than 1 week or off corticosteroids for 2 weeks prior to study enrollment can be enrolled. Enzyme-inducing anti-epileptic drugs are not permitted.
• Patients with a known history of retinal vein occlusion (RVO), central serous retinopathy (CSR), uncontrolled glaucoma or ocular hypertension.
• Patients with class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• Corrected QT (QTc) interval greater than or equal to 480 msecs (\>= 500 msec for subjects with Bundle Branch Block).
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous (IV) antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women and nursing women are excluded from this study because dabrafenib has the potential for teratogenic or abortifacient effects. In embroyfetal developmental studies in rats, developmental toxicities including reduced fetal body weight, embryo-lethality, cardiac ventricular septal defect malformations, delayed skeletal development and variation in thymic shape have been observed.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Univ of Texas-M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

dabrafenib; Radiotherapy, Intensity-Modulated; trametinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Sasan Fazeli, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sasan Fazeli, MD

CONTACT

626-359-8111; sfazeli@coh.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2019
• First Posted: June 5, 2019
• Study Start: September 14, 2020
• Primary Completion (Estimated): October 5, 2027
• Study Completion (Estimated): October 5, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)