Study of Targeted Therapy vs. Chemotherapy in Patients With Thyroid Cancer

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorECOG-ACRIN Cancer Research Group

About this trial

This phase III trial compares the effect of cabozantinib versus combination dabrafenib and trametinib for the treatment of patients with differentiated thyroid cancer that does not respond to treatment (refractory) and which expresses a BRAF V600E mutation. Cabozantinib is in a class of medications called receptor tyrosine kinase inhibitors. It binds to and blocks the action of several enzymes which are often over-expressed in a variety of tumor cell types. This may help stop or slow the growth of tumor cells and blood vessels the tumor needs to survive. Dabrafenib is an enzyme inhibitor that binds to and inhibits the activity of a protein called B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. Trametinib is also an enzyme inhibitor. It binds to and inhibits the activity of proteins called MEK 1 and 2, which play a key role in activating pathways that regulate cell growth. This may inhibit the growth of tumor cells mediated by these pathways. The usual approach for patients with thyroid cancer is targeted therapy with dabrafenib and trametinib. This trial may help researchers decide which treatment option (cabozantinib alone or dabrafenib in combination with trametinib) is safer and/or more effective in treating patients with refractory BRAF V600E-mutated differentiated thyroid cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient must be ≥ 18 years of age

Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Papillary thyroid carcinoma including histological variants of papillary thyroid carcinoma (PTC) such as follicular variant, tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin-like, trabecular, tumor with nodular fasciitis-like stroma, Hürthle cell variant of papillary carcinoma, poorly differentiated.

Follicular thyroid carcinoma including histological variants of follicular thyroid carcinoma (FTC) such as Hürthle cell, clear cell, insular, and poorly differentiated

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Cabozantinib

    Drug

    Given PO

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Dabrafenib

    Drug

    Given PO

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Questionnaire Administration

    Other intervention

    Ancillary study

  • Trametinib

    Drug

    Given PO

Treatment groups

264 Participants
are divided into 2 treatment groups
Group A: Arm A (Dabrafenib and trametinib)Active comparator 6 interventions
Group B: Arm B (Cabozantinib)Experimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS)

PFS will be compared between the two groups using a stratified log-rank test with one-sided type I error of 0.05. Median PFS and 95% confidence interval (CI) for each treatment arm will be estimated using the Kaplan-Meier method. The stratified hazard ratio and 95% CI will be estimated using a Cox proportional hazard model with treatment group as the independent variable.

Time frame
From randomization to radiographic progression of disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, up to 5 years

Secondary outcomes

1

Objective response

Will be assessed based on international criteria proposed by the RECIST 1.1 guideline. Response (complete and partial responses) rate will be estimated. Will be compared using the Fisher's exact test.

Time frame
Up to 5 years
2

Overall survival

Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.

Time frame
From randomization to death from any cause, up to 5 years
3

Duration of response

Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.

Time frame
From confirmed response (complete response or partial response) to progression among patients who achieve a response, up to 5 years
4

PFS2

Median and 95% CI will be estimated in each arm using the Kaplan-Meier method.

Time frame
From randomization to progression on subsequent therapy or death from any cause, up to 5 years

Other outcomes

1

Patient tolerability

Will assess patients tolerability of treatment using the Functional Assessment of Cancer Therapy-General (FACT G)7 and general quality of life using the FACT-GP.

Time frame
At baseline, 4, 8, 16, and 28 weeks
2

Treatment effect

The corresponding 95% CIs will be provided.

Time frame
Up to 5 years
3

Treatment effect by sex

The corresponding 95% CIs will be provided.

Time frame
Up to 5 years
4

Treatment effect by race

The corresponding 95% CIs will be provided.

Time frame
Up to 5 years

Sponsors and contacts

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