Enhancing Radioiodine (RAI) Incorporation Into BRAF Mutant, RAI-Refractory Thyroid Cancers With the BRAF Inhibitor Vemurafenib: A Pilot Study

NCT02145143 | Completed Early Phase 1 FDA Drug

• 1 other identifier: 14-031
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, a drug called vemurafenib, either alone or combined with another treatment called radioactive iodine, has on the patient and thyroid cancer. It is not known if vemurafenib works against thyroid cancer. This study will test in a small number of patients if it can be used with radioactive iodine to treat thyroid cancers. This type of study is called a pilot study. If the results are positive, a larger study with more patients may be done to further test this treatment.

Conditions

Thyroid Carcinoma

Keywords

Radioiodine (RAI) Incorporation; Vemurafenib; 14-031

Outcome Measures

Primary Outcomes (1)

• Response

  The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.

  1 year

Secondary Outcomes (2)

• objective response rate (ORR)

  6 months

• safety

  1 year

Study Arms (1)

thyroid cancer patients

EXPERIMENTAL

Patients will have lesional dosimetry with 124I PET/CT performed to quantify the baseline iodine avidity of index metastatic lesion(s). Patients will then receive vemurafenib (960 mg orally BID) for about 4 weeks, after which a second 124I PET/CT will be performed. For patients in whom the second 124I PET/CT demonstrates that \> or = 2000 cGy can be achieved in at least one tumor with \< 300 mCi of 131I, Thyrogen-stimulated standard dosimetry \& therapeutic 131I will be performed/administered concurrently with vemurafenib. The drug will then be discontinued \& tumor assessments will be conducted with serial radiologic scan(s) \& thyroglobulins (scans will be performed at baseline, before 131I, 3-4 months following 131I, \& 6 months after 131I). Patients whose tumors fail to demonstrate adequate iodine incorporation following vemurafenib to warrant 131I therapy, the study drug will be discontinued, a final tumor assessment will be performed, \& the patient will be taken off the study.

Drug: Vemurafenib; Device: serial 124I PET/CT; Drug: thyrotropin alpha

Interventions

Vemurafenib DRUG

Also known as: RO5185426,, PLX4032, RG7204

thyroid cancer patients

serial 124I PET/CT DEVICE

thyroid cancer patients

thyrotropin alpha DRUG

Also known as: Thyrogen, Genzyme

thyroid cancer patients

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed thyroid carcinoma of follicular origin (including papillary, follicular, or poorly differentiated subtypes and their respective variants).
• Confirmation in a CLIA certified laboratory or in an FDA-approved assay that one of the patient's thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
• RAI-refractory disease on structural imaging, defined as any one of the following:
• A metastatic lesion that is not radioiodine-avid on a diagnostic radioiodine scan performed up to 2 years prior to enrollment in the current study, or
• A radioiodine-avid metastatic lesion which remained stable in size or progressed despite radioiodine treatment 6 months or more prior to entry in the study. There are no size limitations for the index lesion used to satisfy this entry criterion.
• The presence of at least one fluorodeoxyglucose (FDG) avid lesion with a SUVmax ≥ 5.
• No recent treatment for thyroid cancer as defined as:
• No prior 131I therapy is allowed \< 6 months prior to initiation of therapy on this protocol. A diagnostic study using \< 10 mCi of 131I is not considered 131I therapy.
• No external beam radiation therapy \< 4 weeks prior to initiation of therapy on this protocol. (Previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol.)
• No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed \< 4 weeks prior to the initiation of therapy on this protocol.
• Age ≥ 18 years.
• ECOG performance status ≤ 2 (or Karnofsky ≥60%
• Life expectancy of greater than 3 months.
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.

You may not qualify if:

• Concomitant malignancies or previous malignancies within the last 3 years. Exception: Patients who have been disease-free for 3 years, patients with a history of completely resected non-melanoma skin cancer, and/or patients with indolent secondary malignancies, are eligible.
• Use of other investigational drugs within 28 days preceding the first dose of vemurafenib during this study.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to vemurafenib or thyrotropin alpha (Thyrogen).
• History or evidence of cardiovascular risk including any of the following:
• Corrected QT (QTc) interval ≥ 450 msec at baseline or history of congenital long QT syndrome or uncorrectable electrolyte abnormalities
• History or evidence of current, clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to the initiation of therapy on this protocol are eligible).
• History of acute coronary syndromes (specifically, myocardial infarction and unstable angina), severe/unstable angina, coronary angioplasty, or stenting within 6 months prior to the initiation of therapy on this protocol.
• History of symptomatic congestive heart failure within 6 months prior to the initiation of therapy on this protocol.
• History of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant, lactating, or breast feeding women.
• Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone).
• Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration. Those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration.
• Unwillingness or inability to comply with study and follow-up procedures.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Dunn LA, Sherman EJ, Baxi SS, Tchekmedyian V, Grewal RK, Larson SM, Pentlow KS, Haque S, Tuttle RM, Sabra MM, Fish S, Boucai L, Walters J, Ghossein RA, Seshan VE, Ni A, Li D, Knauf JA, Pfister DG, Fagin JA, Ho AL. Vemurafenib Redifferentiation of BRAF Mutant, RAI-Refractory Thyroid Cancers. J Clin Endocrinol Metab. 2019 May 1;104(5):1417-1428. doi: 10.1210/jc.2018-01478.

  PMID: 30256977 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Thyroid Neoplasms; Heterotaxy Syndrome

Interventions

Vemurafenib; Thyrotropin Alfa

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Splenic Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thyrotropin; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Alan L. Ho, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 22, 2014
• Study Start: May 20, 2014
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: June 18, 2025

Record last verified: 2024-11

Locations

US (1)