Medullary Thyroid CancerPhase 2NCT03838692
Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer
A Phase 2 study testing Ponatinib in people with Medullary Thyroid Cancer, run by Antonio Fojo.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Medullary Thyroid Cancer
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 26 Jul 2019to 14 Jun 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
About this study
Official title: A Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer (MTC)
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.
Read the 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.
- Conditions
- Medullary Thyroid Cancer
- Being tested
- Ponatinib
- Keywords
- Ponatinib, Metastatic Medullary, Advanced Medullary
- Medical subject headings
- Carcinoma, Medullary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called ICLUSIG
A daily oral dose at 30 mg.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (1)
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start26 Jul 2019
- Primary completion14 Jun 2021
- Study completion14 Jun 2021
Why it stopped: Closed by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Medullary Thyroid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Antonio Fojo
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor-investigator, Antonio Fojo, Columbia University
- Investigators
- Antonio Fojo, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03838692
- Sponsor's protocol ID
- AAAR5196
- Status last verified
- Oct 2021
- First submitted
- 11 Feb 2019
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer (MTC)
- ClinicalTrials.gov ID
- NCT03838692
- Acronym / sponsor ID
- AAAR5196
- Conditions
- Medullary Thyroid Cancer
- Keywords
- Ponatinib, Metastatic Medullary, Advanced Medullary
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Closed by sponsor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Antonio FojoUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 26 Jul 2019 (actual)
- Primary completion
- 14 Jun 2021 (actual)
- Study completion
- 14 Jun 2021 (actual)
- First posted
- 12 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ponatinib Arm | Experimental | Drug: PonatinibPonatinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PonatinibAlso: ICLUSIGA daily oral dose at 30 mg. | Drug | Ponatinib Arm |
Primary outcome
Objective Response Rate (ORR)
Time frame: 24 months
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.
1 secondary outcome
Progression-Free Survival (PFS)
Time frame: 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Fojo, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ponatinib in people with Medullary Thyroid Cancer, run by Antonio Fojo.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.