Ceritinib in Mutation and Oncogene Directed Therapy in Thyroid Cancer

NCT02289144 | Withdrawn Phase 2 DMC

• 1 other identifier: STU 082014-029
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. Secondary Endpoints:

1. 1.Overall response rate for patients treated with ceritinib as part of the study.
2. 2.Death of study participant due to any cause.

Conditions

Metastatic Anaplastic Thyroid Cancer; Locally Advanced Anaplastic, Undifferentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Development of Progression

  Ceritinib will be administered to the patient until disease progression by RECIST (Response Evaluation Criteria In Solid Tumors).

  Radiographic Imaging Assessments at Screening and every 56 days until evidence of progression (average 7 months) or unacceptable toxicity, withdrawal of Consent, or discontinuation of the trial for any other reason.

Study Arms (1)

Ceritinib

EXPERIMENTAL

Drug: Ceritinib

Interventions

Ceritinib DRUG

750 mg orally daily on day 1. Continue every 4 weeks and every 2 cycles (1 Cycle is 28 days long) : until progression, new recurrence or distant metastasis, as well as enlargment of an existing metastasis on radiological Imaging.

Ceritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients will not have any other curative therapeutic option, such as radiation or surgery.
• WHO performance status 0-2.
• Age greater then or equal to 18 years.
• 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.
• 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
• Aspartate transaminase (AST) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if AST \< 3 x ULN; alanine transaminase (ALT) \< 2.0 x ULN, except for patients with liver metastasis, who are only included if ALT \< 3 x ULN
• Calculated or measured creatinine clearance (CrCL) less then or equal to 30 mL/min
• Patient must have the following laboratory values or have the following laboratory values corrected with supplements to be within normal limits at screening:
• Potassium ≥ LLN
• Magnesium ≥ LLN

You may not qualify if:

• Patients eligible must not meet any of the following criteria:
• Patients with known hypersensitivity to any of the excipients of ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate).
• 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.
• Prior therapy with ceritinib.
• 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).
• 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);
• uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without antihypertensive medication
• initiation or adjustment of antihypertensive medication(s) is allowed prior to screening;
• ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication;
• other cardiac arrhythmia not controlled with medication;
• corrected QTc \> 450 msec using Fridericia correction on the screening ECG
• Impaired GI function or GI disease that may alter absorption of ceritinib or inability to swallow up to five ceritinib capsules daily.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Novartis: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic

Interventions

ceritinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Saad A Khan, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: November 13, 2014
• Study Start: June 1, 2015
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: July 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)