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Ceritinib in Mutation and Oncogene Directed Therapy in Thyroid Cancer | Clinical Trials | Clareo Health

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Ceritinib in Mutation and Oncogene Directed Therapy in Thyroid Cancer

Ceritinib in Mutation and Oncogene Directed Therapy in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer

NCT02289144•University of Texas Southwestern Medical Center

View on ClinicalTrials.gov

Summary

Detailed Description

This is an, open-label, protocol designed to evaluate the activity of targeted therapy in anaplastic/undifferentiated thyroid cancer. Arm A will evaluate ATC/UTC with mutations or rearrangements detected in the ALK gene. There is no effective treatment for anaplastic thyroid cancer in the locally recurrent or metastatic setting. Ceritinib will be administered to the patient until disease progression by RECIST 1.1, unacceptable toxicity, withdrawal of consent, or discontinuation of the trial for any other reason. The primary focus of this arm of the protocol is identifying ceritinib's activity in anaplastic or undifferentiated thyroid cancer patients. Those patients with mutations identified in their ALK gene by sequencing their tumor samples, or with the established ALK abnormalities will be treated with ALK-inhibitors. These include the Ventana assay and Vysis FISH probe, and patients with tumors positive by this assay will also be considered eligible for therapy on the trial. The goal of this multi-center, multi-arm trial is to measure the impact of treating metastatic anaplastic thyroid cancer patients with targeted therapy selected for these patients due the presence of a genetic mutation or other aberration. This trial will serve as a framework by which new biomarker-drug combinations can be identified and added as new arms. Therapeutic Portion: ARM A: ALK Abnormality IND Ceritinib 750 mg orally daily on Day 1 Continue q4 weeks x 2 cycles Primary Endpoint: The development of progression; new recurrence or distant metastasis, as well as enlargement of an existing metastasis on radiographic imaging. CT scans of the neck, chest, abdomen and pelvis will be performed at baseline and every two cycles (cycles are 28 days long) according to standard of care. Other imaging of these areas such as PET/MRI will be allowed if CT cannot be performed. MRI of the brain will be performed at baseline and as clinically indicated. Wherever it can be safely given, radiographic contrast agents should be given for the imaging studies. Secondary Endpoints: 1. Overall response rate for patients treated with ceritinib as part of the study. 2. Death of study participant due to any cause.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer that demonstrates mutation in the ALK gene as assessed by sequencing of the tumor specimen for Arm A. Other ALK abnormalities as detected by the approved FISH test (Abbott Molecular Inc), using Vysis breakapart probes (defined as 15% or more positive tumor cells); or the Ventana IHC test will also be seen as evidence of ALK abnormality and meeting eligibility requirement.
•2. Patients will not have any other curative therapeutic option, such as radiation or surgery.
•3. WHO performance status 0-2.
•4. Age greater then or equal to 18 years.
•5. Patients must have recovered from all toxicities related to prior anticancer therapies to ≤ Grade 2 (CTCAE v 4.03), provided that any concomitant medication is given prior to initiation of treatment with ceritinib. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
•6. Adequate organ function: the following laboratory criteria have been met:
•* Absolute neutrophil count (ANC) greater then or equal to 1.5 x 109/L
•* Hemoglobin (Hgb) ≥ 8 g/dL
•* Platelets greater then or equal to 75 x 109/L
•* Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN), except for patients with Gilbert's syndrome who may be included if total bilirubin ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
+9 more criteria

Exclusion Criteria

•Patients eligible must not meet any of the following criteria:
•1. Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
•2. Patients with symptomatic CNS metastases who are neurologically unstable or have required increasing doses of steroids within the 1 week prior to study entry to manage CNS symptoms.
•3. Prior therapy with ceritinib.
•4. Presence or history of a malignant disease other than thyroid cancer that has been diagnosed and/or required therapy within the past year and is undergoing active anticancer treatment. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
•5. Patients with known history of extensive disseminated bilateral interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, obliterative bronchiolitis, and clinically significant radiation pneumonitis (i.e. affecting activities of daily living or requiring therapeutic intervention).
•6. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:
•* unstable angina within 6 months prior to screening;
•* myocardial infarction within 6 months prior to screening;
•* history of documented congestive heart failure (New York Heart Association functional classification III-IV);
+27 more criteria

Locations (1)

UT Southwestern Medical Center

Dallas, Texas, United States

Key Dates

Start Date

June 1, 2015

Primary Completion Date

January 1, 2019

Completion Date

January 1, 2019

Last Updated

July 30, 2019

Conditions

Metastatic Anaplastic Thyroid CancerLocally Advanced Anaplastic, Undifferentiated Thyroid Cancer

Interventions

Ceritinib

DRUG