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

NCT02456701 | Completed Phase 1

• 1 other identifier: KTN3379-CL-003
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Thyroid Cancer

Keywords

CDX3379

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Safety and tolerability of the combination of vemurafenib and KTN3379 by assessing adverse events

  6 to 8 weeks

Other Outcomes (3)

• The ORR by RECIST v1.1 criteria at 6 months following treatment with vemurafenib and KTN3379 plus 131I

  6 months

• The proportion of patients alive at 6 months without disease progression by RECIST v1.1 criteria following treatment with vemurafenib and KTN3379 plus 131I

  6 months

• Changes in thyroglobulin levels in patients treated with 131I

  6 months

Study Arms (1)

Combination of Vemurafenib and KTN3379

EXPERIMENTAL

Vemurafenib 960 mg po bid KTN3379 1000 mg IV q2weeks

Biological: KTN3379; Drug: vemurafenib

Interventions

KTN3379 BIOLOGICAL

IV every 2 weeks

Combination of Vemurafenib and KTN3379

vemurafenib DRUG

960 mg po bid

Also known as: Zelboraf

Combination of Vemurafenib and KTN3379

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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celldex Therapeutics: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Tchekmedyian V, Dunn L, Sherman E, Baxi SS, Grewal RK, Larson SM, Pentlow KS, Haque S, Tuttle RM, Sabra MM, Fish S, Boucai L, Walters J, Ghossein RA, Seshan VE, Knauf JA, Pfister DG, Fagin JA, Ho AL. Enhancing Radioiodine Incorporation in BRAF-Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial. Thyroid. 2022 Mar;32(3):273-282. doi: 10.1089/thy.2021.0565.

  PMID: 35045748 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Vemurafenib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 28, 2015
• Study Start: June 1, 2015
• Primary Completion: October 13, 2016
• Study Completion: October 13, 2016
• Last Updated: September 5, 2017

Record last verified: 2017-08

Locations

US (1)