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Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

Primary Purpose

Medullary Thyroid Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ponatinib
Sponsored by
Antonio Fojo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medullary Thyroid Cancer focused on measuring Ponatinib, Metastatic Medullary, Advanced Medullary

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Ponatinib Arm

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Progression-Free Survival (PFS)
    PFS is defined as the time from the first day of trial treatment to the first documented disease progression per the Kaplan-Meier curve.

    Full Information

    First Posted
    February 11, 2019
    Last Updated
    October 6, 2021
    Sponsor
    Antonio Fojo
    Collaborators
    Millennium Pharmaceuticals, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03838692
    Brief Title
    Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer
    Official Title
    A Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer (MTC)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2021
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Closed by sponsor
    Study Start Date
    July 26, 2019 (Actual)
    Primary Completion Date
    June 14, 2021 (Actual)
    Study Completion Date
    June 14, 2021 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Antonio Fojo
    Collaborators
    Millennium Pharmaceuticals, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Medullary Thyroid Cancer
    Keywords
    Ponatinib, Metastatic Medullary, Advanced Medullary

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ponatinib Arm
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Ponatinib
    Other Intervention Name(s)
    ICLUSIG
    Intervention Description
    A daily oral dose at 30 mg.
    Primary Outcome Measure Information:
    Title
    Objective Response Rate (ORR)
    Description
    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.
    Time Frame
    24 months
    Secondary Outcome Measure Information:
    Title
    Progression-Free Survival (PFS)
    Description
    PFS is defined as the time from the first day of trial treatment to the first documented disease progression per the Kaplan-Meier curve.
    Time Frame
    24 months
    Other Pre-specified Outcome Measures:
    Title
    Total Number of Adverse Reactions
    Description
    Testing safety and toxicity assessed using CTCAE criteria
    Time Frame
    24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Fojo, MD
    Organizational Affiliation
    Columbia University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer

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