Pioglitazone in Follicular or Follicular Variant of Papillary Thyroid Cancers

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Michigan
Sponsor:
Information provided by (Responsible Party):
Ronald J. Koenig, MD PhD, University of Michigan
ClinicalTrials.gov Identifier:
NCT01655719
First received: July 25, 2012
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Follicular Thyroid Carcinoma
Follicular Variant of Papillary Thyroid Carcinoma
Drug: Pioglitazone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of Pioglitazone in Follicular-patterned Thyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Tumor response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Determine the overall response (complete and partial response) rates of patients with PAX8-PPARgamma fusion gene-positive follicular-patterned thyroid carcinomas treated with pioglitazone.


Secondary Outcome Measures:
  • Decrease in serum thyroglobulin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Determine if pioglitazone decreases serum thyroglobulin in patients with follicular-patterned thyroid carcinomas that contain the PAX8-PPARgamma fusion gene.

  • Toxicity [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Measure toxicities experienced by patients with PAX8-PPARgamma fusion gene-positive follicular-patterned thyroid carcinomas treated with pioglitazone.


Other Outcome Measures:
  • Biomarkers [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Define predictive markers of response or insensitivity to pioglitazone. Unstained tumor tissue slides from archival paraffin blocks, fresh biopsy specimens from measurable metastases, and blood samples (serum and peripheral blood cells) will be collected on enrolled patients who consented for the optional correlative studies. These will be used to identify factors that predict efficacy of pioglitazone. Analyses may include measures of expression of specific RNAs and proteins, and DNA sequence analysis.

  • Sensitization to radioiodine therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Determine if pioglitazone induces a clinically significant level of radioiodine uptake in the residual thyroid carcinoma, and if so, whether there is a therapeutic response to radioiodine. This will be addressed in a separate follow-up protocol available to subjects completing this study.

  • Lipid accumulation in tumor [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Determine (by MRI) if pioglitazone induces lipid accumulation in follicular-patterned thyroid carcinomas that contain the PAX8-PPARgamma fusion gene.


Estimated Enrollment: 15
Study Start Date: April 2012
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pioglitazone Treatment

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.

Drug: Pioglitazone

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically confirmed follicular thyroid carcinoma or follicular variant of papillary 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.

  2. Measurable disease by RECIST 1.1 criteria.
  3. Documented disease progression by RECIST 1.1 in the past 14 months.
  4. Availability of histological material (primary tumor or metastases) for review of the diagnosis and demonstration of PAX8-PPARgamma fusion gene.
  5. Adequate TSH suppression (<0.5 mIU/L)
  6. Prior chemotherapy or surgery must have been completed at least 28 days prior to registration, and all toxicities must have resolved.
  7. 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.
  8. Age 18 - 75 years of age
  9. Life expectancy of greater than 6 months.
  10. ECOG performance status 2 or less.
  11. 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)

  12. Patients must be able to consume oral medications.
  13. 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).
  14. All patients must sign an informed consent prior to enrollment.

Exclusion Criteria:

  1. Patients may not be receiving any other investigational agents.
  2. Patients with known untreated brain metastases.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to pioglitazone.
  4. 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
  5. Therapy with rosiglitazone (Avandia) or pioglitazone (Actos) at any time since the diagnosis of thyroid cancer.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure, unstable angina pectoris, or cardiac arrhythmias.
  7. 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.
  8. No concurrent radiotherapy or chemotherapy may be given to the patient during the administration of the study drug.
  9. Patients with uncontrolled malabsorption syndromes.
  10. Patients with a history of congestive heart failure of any New York Heart Association class.
  11. Any medical or psychiatric illness which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment regimen.
  12. Use of rifampin (strong CYP2C8 inducer) within 14 days of study Day 1.
  13. Other current malignancy than the disease under study.
  14. Grade 2 or worse edema within 14 days of study Day 1, per CTCAE v4.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655719

Contacts
Contact: Timothy Muth, MS 734-615-8914 tmuth@med.umich.edu

Locations
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Lauren Suppes       Lauren.Suppes@UCDenver.edu   
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Timothy Muth, MS       tmuth@med.umich.edu   
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Jennifer Brown       jennifer.brown@osumc.edu   
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Thelma McCloskey       Thelma.McCloskey@uphs.upenn.edu   
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Madonna Pool       MMPool@mdanderson.org   
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Ronald J Koenig, MD, PhD University of Michigan
  More Information

No publications provided

Responsible Party: Ronald J. Koenig, MD PhD, Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01655719     History of Changes
Other Study ID Numbers: 2011.097
Study First Received: July 25, 2012
Last Updated: July 10, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Thyroid Neoplasms
Carcinoma
Thyroid Diseases
Adenocarcinoma, Follicular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Adenocarcinoma
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014