Thyroid Cancers That Contain the PAX8-PPARgamma Fusion GenePhase 2NCT01655719
Pioglitazone in Thyroid Cancers
A Phase 2 study testing Pioglitazone in people with Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene, run by University of Michigan at 4 sites in United States.
Trial summary
Through this trial the investigators hope to learn if a drug, Actos (pioglitazone), is useful in treating a certain kind of metastatic thyroid cancer. Actos is approved by the FDA to treat diabetes. It has not been approved by the FDA to treat cancer, so its use in this study is considered experimental. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene
- What is being tested?
- Pioglitazone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2012to 31 Mar 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have histologically confirmed thyroid carcinoma with the PAX8-PPARgamma translocation (translocation testing will be performed on archived tissue during the screening period).
- Refractory to radioactive iodine (RAI) as defined by: the tumor does not concentrate RAI; or the patient has had RAI within the last 16 months and has had progression despite that RAI; or the last RAI treatment was >16 months ago and the patient progressed after at least two RAI treatments; or the patient has received RAI treatments with a cumulative RAI dose of ≥22.2 GBq (600 mCi)
- Not a candidate for surgery or RAI therapy with curative intent.
- Lesions that would be treated by external beam radiation therapy (EBRT) based on standard of care can be so treated, but then cannot be used as target lesions.
- Measurable disease by RECIST 1.1 criteria.
- Documented disease progression by RECIST 1.1 in the past 14 months.
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- Availability of histological material (primary tumor or metastases) for review of the diagnosis and demonstration of PAX8-PPARgamma fusion gene.
- Adequate TSH suppression (<0.5 mIU/L)
- Prior chemotherapy or surgery must have been completed at least 28 days prior to registration, and all toxicities must have resolved.
- Prior radioactive iodine must have been completed at least 6 months prior to registration, or there must be documented disease progression since such therapy if it was within 6 months. Sites that have received EBRT must have disease progression post-EBRT to be used as sites of measurable disease.
- Life expectancy of greater than 6 months.
- ECOG performance status 2 or less.
- Patients must have normal organ function as defined below:
- AST(SGOT)/ALT(SGPT) less than 2.5 X institutional upper limit of normal (within 1 month of study Day 1)
- Patients must be able to consume oral medications.
- Women of childbearing potential must have a negative pregnancy test at baseline prior to receiving any study drug and must practice effective contraception while on study. (Pregnant or lactating patients are excluded).
- All patients must sign an informed consent prior to enrollment.
Who cannot join
- Patients may not be receiving any other investigational agents.
- Patients with known untreated brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pioglitazone.
- Diagnosis of diabetes mellitus or current therapy with any drugs used to treat diabetes mellitus, including but not limited to insulin, sulfonylureas, metformin, rosiglitazone (Avandia), and pioglitazone (Actos) within 14 days of study Day 1
- Therapy with rosiglitazone (Avandia) or pioglitazone (Actos) at any time since the diagnosis of thyroid cancer.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, or cardiac arrhythmias.
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- Pregnant women are excluded from this study because pioglitazone is a U.S. Food and Drug Administration Pregnancy Category C drug. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pioglitazone, breastfeeding should be discontinued if the mother is treated with pioglitazone.
- No concurrent radiotherapy or chemotherapy may be given to the patient during the administration of the study drug.
- Patients with uncontrolled malabsorption syndromes.
- Patients with a history of congestive heart failure of any New York Heart Association class.
- Any medical or psychiatric illness which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment regimen.
- Use of rifampin (strong CYP2C8 inducer) within 14 days of study Day 1.
- Other current malignancy than the disease under study.
- Grade 2 or worse edema within 14 days of study Day 1, per CTCAE v4.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado
Aurora, Colorado, 80045
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 2 Study of Pioglitazone in Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene
Through this trial the investigators hope to learn if a drug, Actos (pioglitazone), is useful in treating a certain kind of metastatic thyroid cancer. Actos is approved by the FDA to treat diabetes. It has not been approved by the FDA to treat cancer, so its use in this study is considered experimental.
- Being tested
- Pioglitazone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone Treatment | Experimental | If eligible, subjects can participate in 1 or both parts of this study as follows:
Part 1: In the initial main portion of the study subjects will receive 24 -28 weeks of therapy with pioglitazone at the dosage approved for the control of diabetes. Response will be evaluated per RECIST. Safety measure are outlined in the protocol including weekly weigh ins, calls, labs, exams, etc.
Part 2: A secondary protocol is then available to subjects who complete the main initial study with less than complete response per RECIST. They can undergo a radioiodine scan to see if the treatment with pioglitazone has sensitized their disease to radioiodine. If it has - they can pursue the radioiodine treatment. Receives: Drug: Pioglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response (Change)
Response is measured by change in Tumor size (cm)
Measured: Baseline and 24 weeks
Secondary outcomes (2)
Change in Serum Thyroglobulin
Determine if pioglitazone decreases serum thyroglobulin in patients with follicular-patterned thyroid carcinomas that contain the PAX8-PPARgamma fusion gene.
Measured: Baseline and 24 weeks
Toxicity
Toxicities experienced by patients with PAX8-PPARgamma fusion gene-positive follicular-patterned thyroid carcinomas treated with pioglitazone are indicated by presence of Serious Adverse Events (that show relatedness).
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startApr 2012
- Primary completion31 Mar 2017
- Study completion31 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thyroid Cancers That Contain the PAX8-PPARgamma Fusion GeneStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ronald J. Koenig, MD PhD, University of Michigan
- Investigators
- Ronald J Koenig, MD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01655719
- Sponsor's protocol ID
- 2011.097
- Other IDs
- R01CA166033
- Status last verified
- Sep 2017
- First submitted
- 25 Jul 2012
- Last updated
- 26 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Giordano TJ, Haugen BR, Sherman SI, Shah MH, Caoili EM, Koenig RJ. Pioglitazone Therapy of PAX8-PPARgamma Fusion Protein Thyroid Carcinoma. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1277-1281. doi: 10.1210/jc.2017-02533.
PubMed 29373711
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Pioglitazone in Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene
- ClinicalTrials.gov ID
- NCT01655719
- Acronym / sponsor ID
- 2011.097
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2012 (actual)
- Primary completion
- 31 Mar 2017 (actual)
- Study completion
- 31 Mar 2017 (actual)
- First posted
- 2 Aug 2012 (estimated)
- Results
- Posted 26 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Through this trial the investigators hope to learn if a drug, Actos (pioglitazone), is useful in treating a certain kind of metastatic thyroid cancer. Actos is approved by the FDA to treat diabetes. It has not been approved by the FDA to treat cancer, so its use in this study is considered experimental.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone Treatment | Experimental | Drug: PioglitazoneIf eligible, subjects can participate in 1 or both parts of this study as follows: Part 1: In the initial main portion of the study subjects will receive 24 -28 weeks of therapy with pioglitazone at the dosage approved for the control of diabetes. Response will be evaluated per RECIST. Safety measure are outlined in the protocol including weekly weigh ins, calls, labs, exams, etc. Part 2: A secondary protocol is then available to subjects who complete the main initial study with less than complete response per RECIST. They can undergo a radioiodine scan to see if the treatment with pioglitazone has sensitized their disease to radioiodine. If it has - they can pursue the radioiodine treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histologically confirmed thyroid carcinoma with the PAX8-PPARgamma translocation (translocation testing will be performed on archived tissue during the screening period).
- Refractory to radioactive iodine (RAI) as defined by: the tumor does not concentrate RAI; or the patient has had RAI within the last 16 months and has had progression despite that RAI; or the last RAI treatment was >16 months ago and the patient progressed after at least two RAI treatments; or the patient has received RAI treatments with a cumulative RAI dose of ≥22.2 GBq (600 mCi)
- Not a candidate for surgery or RAI therapy with curative intent.
- Lesions that would be treated by external beam radiation therapy (EBRT) based on standard of care can be so treated, but then cannot be used as target lesions.
- Measurable disease by RECIST 1.1 criteria.
Key exclusion criteria (14 listed)
- Patients may not be receiving any other investigational agents.
- Patients with known untreated brain metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pioglitazone.
- Diagnosis of diabetes mellitus or current therapy with any drugs used to treat diabetes mellitus, including but not limited to insulin, sulfonylureas, metformin, rosiglitazone (Avandia), and pioglitazone (Actos) within 14 days of study Day 1
- Therapy with rosiglitazone (Avandia) or pioglitazone (Actos) at any time since the diagnosis of thyroid cancer.
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 |
|---|---|---|
| PioglitazoneAlso: Actos | Drug | Pioglitazone Treatment |
Primary outcome
Tumor Response (Change)
Time frame: Baseline and 24 weeks
Response is measured by change in Tumor size (cm)
2 secondary outcomes
Change in Serum Thyroglobulin
Time frame: Baseline and 24 weeks
Toxicity
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29373711Giordano TJ, Haugen BR, Sherman SI, Shah MH, Caoili EM, Koenig RJ. Pioglitazone Therapy of PAX8-PPARgamma Fusion Protein Thyroid Carcinoma. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1277-1281. doi: 10.1210/jc.2017-02533.
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.
Ronald J Koenig, MD, PhD principal investigator
University of Michigan
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone in people with Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene, run by University of Michigan at 4 sites in United States.
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 17 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: finished, as of the sponsor's last update on 26 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Yes. Results are posted in the registry (first posted 26 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Response (Change) (time frame: Baseline and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01655719, which also lists 1 linked publication.
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 26 Oct 2017.