Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

NCT ID: NCT03838692

Last Updated: 2021-10-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-26
• Study Completion Date: 2021-06-14

Brief Summary

The primary objective of this study is to determine in an exploratory manner the objective overall response rate to ponatinib in the treatment of patients with advanced or metastatic MTC previously treated with cabozantinib or vandetanib who have tumors with rearranged-during-transfection (RET) mutations and have tumors without RET mutations.

Detailed Description

Ponatinib is an investigational agent that blocks abnormal cancer proteins and therefore harms cancer cells. It was recently approved by the Food and Drug Administration for leukemia treatment, but is not approved for medullary thyroid cancer treatment. Early studies, however, have shown that medullary thyroid tumors respond to ponatinib. These studies were done in the laboratory and not performed on humans. This is a study designed for patients with medullary thyroid cancer. Treatment will consist of a drug called ponatinib which is a pill that taken once each day and continue throughout the duration of the study. The purpose of the study is to:

1. Determine if this treatment will be effective in decreasing the amount of cancer and, if it does, to determine how long the response will last.

2. Determine the side effects that may occur with this treatment.

3. To analyze genetic mutations in tumors to help us understand how tumors grow and how these drugs interact with the mechanisms within the tumor.

Ponatinib has been given to many patients with leukemia and is now approved by the United States Food and Drug Administration for treatment of certain types of leukemia. This study will seek to determine if ponatinib can bring benefit to patients with medullary thyroid cancer.

Conditions

Medullary Thyroid Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ponatinib Arm

Ponatinib tablets will be taken by mouth, continuously, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment can be taken with water, with or without food, at approximately the same time each day.

Group Type: EXPERIMENTAL

Ponatinib

Intervention Type: DRUG

A daily oral dose at 30 mg.

Interventions

Ponatinib

A daily oral dose at 30 mg.

Intervention Type: DRUG

Other Intervention Names

ICLUSIG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of localized or metastatic unresectable MTC.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computerized tomography (CT) scan.
• The last dose of previous therapy targeting RET kinase must be given at least 4 weeks - Previous treatment with cytotoxic chemotherapy, immunotherapy, or radiotherapy are permitted, if the last dose was given at least 4 weeks prior to the first dose of ponatinib
• Patient must have failed (progressed on or been intolerant of) prior treatment with cabozantinib or vandetanib.
• Age ≥18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Normal organ and marrow function as defined below:
• Negative pregnancy test for women of childbearing potential or male patients, even if surgically sterilized (i.e., status post-vasectomy), who:

• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
• Agree to completely abstain from heterosexual intercourse
• Normal QT interval corrected on screening electrocardiogram (ECG) evaluation, defined as the corrected QT interval by Fredericia (QTcF) of ≤450 ms.
• Ability to understand and the willingness to sign a written informed consent document and follow the guidelines of the clinical protocol including visits for treatment and follow up
• Life expectancy of greater than 12 weeks
• Available archival tissue or willingness to undergo fresh biopsy if no archival tissue is available.

Exclusion Criteria

• Patients who are receiving any other investigational agent.
• Patients with brain metastases or spinal cord compression unless they completed radiation therapy ≥4 weeks prior to the first dose of ponatinib and are stable without steroids or anti-convulsant therapy for ≥10 days.
• Patients who cannot discontinue medications that are known to be associated with Torsades de Pointes. These medications are listed in Attachment 3
• Uncontrolled hypertension (systolic blood pressure >150 or diastolic blood pressure >100
• Significant or active cardiovascular disease within 6 months prior to enrollment
• A history of pancreatitis or alcohol abuse
• Uncontrolled hypertriglyceridemia (>450 mg/dL)
• Major surgery (with the exception of minor surgical procedures, such as catheter placement or tumor biopsy) within 28 days prior to the first dose of ponatinib
• Ongoing or active infection including known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C (HCV). Testing for these viruses is not required in the absence of a history of infection.
• Suffer from any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the study drug
• Evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement
• Presence of another primary malignancy within the past 2 years (except for non-melanoma skin cancer or cervical cancer in situ. Prior prostate cancer is also permitted if prostate-specific antigen (PSA) is now undetectable)
• Pregnant or lactating
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to investigational agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Antonio Fojo

OTHER

Sponsor Role: lead

Responsible Party

Antonio Fojo

Assistant Professor of Medicine at the Columbia University Medical

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Antonio Fojo, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Other Identifiers

AAAR5196

Identifier Type: -

Identifier Source: org_study_id