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

Phase 1

Completed

• Conditions: Thyroid Cancer
• Interventions: Biological: KTN3379; Drug: vemurafenib

• Registration Number: NCT02456701
• Lead Sponsor: Celldex Therapeutics

Brief 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.

Detailed Description

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. Eligible patients with BRAF MUT, RAIR thyroid cancer will undergo human recombinant TSH (rhTSH or Thyrogen)-stimulated 124I PET/CT lesional dosimetry to quantify the baseline RAI avidity of index metastatic lesion(s). Patients will then receive vemurafenib followed by the addition of KTN3379 after which a second Thyrogen-stimulated 124I PET/CT lesional dosimetry will be performed. For patients whose tumor(s) demonstrate sufficient iodine incorporation warranting 131I therapy, Thyrogen-stimulated standard dosimetry will be performed and therapeutic 131I will be administered concurrently with vemurafenib and KTN3379. Subsequent to discontinuation of vemurafenib, tumor assessments will be conducted with serial radiologic scan(s) and thyroglobulins (scans will be performed at baseline, before 131I, 3 months (+/- 1 month) following 131I, and 6 months after 131I).

Study Timeline

• Study First Submitted: 2015-05-20
• Study First Submitted QC: 2015-05-26
• Study First Posted: 2015-05-28
• Study Start: 2015-06
• Primary Completion: 2016-10-13
• Study Completion: 2016-10-13
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-31
• Last Update Posted: 2017-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Vemurafenib and KTN3379	KTN3379	Vemurafenib 960 mg po bid KTN3379 1000 mg IV q2weeks
Combination of Vemurafenib and KTN3379	vemurafenib	Vemurafenib 960 mg po bid KTN3379 1000 mg IV q2weeks

Primary Outcome Measures

Name	Time	Method
The number of patients with BRAF MUT, radioiodine-refractory thyroid cancer in which the combination of vemurafenib and KTN3379 can increase tumoral iodine incorporation to warrant 131I treatment	4 to 6 weeks

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of the combination of vemurafenib and KTN3379 by assessing adverse events	6 to 8 weeks

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States