Enhancing Radioiodine Incorporation Into BRAF Mutant Thyroid Cancers With the Combination of Vemurafenib and KTN3379

• Status: Completed
• Trial end date: 2016-10-13
• Target enrollment: 0
• Participant gender: All

Summary

This is a patient pilot study testing the hypothesis that vemurafenib with the addition of KTN3379 can restore iodine incorporation in BRAF mutant (MUT), radioiodine-refractory (RAIR) thyroid cancer patients.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celldex Therapeutics
• Collaborator: Memorial Sloan Kettering Cancer Center
• Treatments: Vemurafenib

Criteria

Inclusion Criteria:

• 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 by RECIST criteria 1.1.

• 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

• Age ≥ 18 years.

• ECOG performance status ≤ 2

• Patients must have normal organ and marrow function as defined below:

• Absolute neutrophil count (ANC) > 1500/mcl

• Hemoglobin ≥ 9 g/dL

• Platelets ≥ 100,000/mcl

• Albumin ≥ 2.5 g/dL

• Total bilirubin ≤ 1.5x institutional ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x institutional ULN unless it is related to the primary disease

• Creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min OR 24-hour urine creatinine clearance ≥ 50 mL/min

Exclusion Criteria:

• Concomitant malignancies or previous malignancies treated within the past 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 on this study.

• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.

• 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. (Patients with well controlled atrial fibrillation are exempt from this criteria.)

• 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.