Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

NCT03838692 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: AAAR5196
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Medullary Thyroid Cancer

Keywords

Ponatinib; Metastatic Medullary; Advanced Medullary

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST.

  24 months

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  24 months

Other Outcomes (1)

• Total Number of Adverse Reactions

  24 months

Study Arms (1)

Ponatinib Arm

EXPERIMENTAL

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.

Drug: Ponatinib

Interventions

Ponatinib DRUG

A daily oral dose at 30 mg.

Also known as: ICLUSIG

Ponatinib Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Antonio Fojo: lead
• Millennium Pharmaceuticals, Inc.: collaborator

MeSH Terms

Conditions

Carcinoma, Medullary

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms, Nerve Tissue

Study Officials

• Antonio Fojo, MD

  Columbia University

  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 INVESTIGATOR
• PI Title: Assistant Professor of Medicine at the Columbia University Medical

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 12, 2019
• Study Start: July 26, 2019
• Primary Completion: June 14, 2021
• Study Completion: June 14, 2021
• Last Updated: October 13, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share