Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00085293
First received: June 10, 2004
Last updated: August 20, 2014
Last verified: May 2014
  Purpose

This phase II trial is studying how well decitabine works in treating patients with metastatic papillary thyroid cancer or follicular thyroid cancer that has stopped responding to radioactive iodine. Iodine I 131 (radioactive iodine) kills thyroid cancer cells. Metastatic thyroid cancer cells can lose the ability to be treated with radioactive iodine. Decitabine may help thyroid cancer cells regain the ability to respond to treatment with radioactive iodine.


Condition Intervention Phase
Recurrent Thyroid Cancer
Stage IVA Follicular Thyroid Cancer
Stage IVA Papillary Thyroid Cancer
Stage IVB Follicular Thyroid Cancer
Stage IVB Papillary Thyroid Cancer
Stage IVC Follicular Thyroid Cancer
Stage IVC Papillary Thyroid Cancer
Drug: Decitabine
Radiation: Iodine I 131
Biological: Recombinant thyrotropin alfa
Radiation: Fludeoxyglucose F 18
Procedure: Positron emission tomography
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 II Study of Decitabine in Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration [ Time Frame: Week 3 following 2 weeks of Decitabine therapy ] [ Designated as safety issue: No ]

    Number of participants with restoration of radioiodine responsiveness as determined by visible uptake on radioiodine scan in radiographically detectable metastatic foci of papillary or follicular thyroid carcinoma. Response to Decitabine defined as demonstration of radioiodine uptake determined by centralized blinded review of diagnostic scan. All who demonstrated radioiodine uptake in metastatic foci following decitabine therapy would then undergo thyroid hormone withdrawal and a second course of decitabine in preparation for therapeutic administration of radioiodine.

    Diagnostic radioiodine scans following decitabine therapy (week 3) with a radioiodine scan following thyrotropin alfa stimulation, 0.9 mg intramuscular (IM) injection 24 and 48 hours before administration of the 131I for imaging. Whole body scans (WBS) performed using a gamma camera.



Secondary Outcome Measures:
  • Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Efficacy of Subsequent Radioiodine Therapy in Terms of Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) of Any Radiographic Disease [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  • Efficacy of Subsequent Radioiodine Therapy in Terms of CR/PR/SD of Any Radiographic Disease [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  • Change in Fludeoxyglucose (FDG) Uptake Measured by Positron Emission Tomography (PET) in Metastatic Tumor Sites Before and After DNA-methyltransferase Inhibitor Therapy (Optional) [ Time Frame: Baseline to 3 weeks ] [ Designated as safety issue: No ]
  • Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    Summary of Adverse Events (AEs) by Maximum Grade where Grade 1 AEs >20%, Grade 2 AEs >10%, all Grade 3, Grade 4 and Grade 5 reported.


Enrollment: 12
Study Start Date: May 2004
Study Completion Date: May 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Starting dose 6 mg/m^2 Decitabine intravenous (IV) over 1 hour on days 1-5 and 8-12 of weeks 1 and 2 (course 1). Week 3, Iodine I 131 (131I) scanning using thyrotropin alfa injections. Participants whose scan do not demonstrate iodine uptake continue suppressive thyroid hormone therapy but no further study therapy; these participants who do show uptake undergo thyroid hormone withdrawal on weeks 4-8 and second course of decitabine (as in course 1) on weeks 7 and 8, with 131I therapy on week 9.
Drug: Decitabine
Starting dose 6 mg/m^2 intravenously over 1 hour every day for 5 successive days for 2 weeks (10 doses), with possible second course.
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Radiation: Iodine I 131
Undergo thyrotropin-alfa stimulated radioactive iodine scan
Other Names:
  • I 131
  • Iodotope
  • Iodotrope
Biological: Recombinant thyrotropin alfa
Undergo thyrotropin-alfa stimulated radioactive iodine scan
Other Name: Thyrogen
Radiation: Fludeoxyglucose F 18
Optional correlative studies
Other Names:
  • 18FDG
  • FDG
Procedure: Positron emission tomography
Optional correlative studies
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed

Detailed Description:

PRIMARY OBJECTIVE:

I. Determine whether decitabine can restore iodine I 131 (131I) uptake in patients with metastatic papillary thyroid or follicular thyroid cancer lesions that are undetectable by low-dose iodine 131I scanning.

SECONDARY OBJECTIVES:

I. Determine the efficacy of 131I therapy, administered after restoration of 131I uptake by decitabine, in these patients.

II. Determine the effect of decitabine on clinical and molecular markers of thyroid cancer cell differentiation in these patients.

III. Determine the safety and tolerability of decitabine in patients undergoing thyroid hormone withdrawal-induced hypothyroidism and 131I therapy.

OUTLINE: This is an open-label, multicenter study.

Patients receive decitabine intravenous (IV) over 1 hour on days 1-5 and 8-12 of weeks 1 and 2 (course 1). On week 3, patients undergo iodine I 131 (131I) scanning using thyrotropin alfa injections. Patients whose scan does not demonstrate iodine uptake continue suppressive thyroid hormone therapy but receive no further study therapy. These patients undergo study follow up.

Patients whose scan demonstrates iodine uptake undergo thyroid hormone withdrawal on weeks 4-8 and receive a second course of decitabine (as in course 1) on weeks 7 and 8. Patients then receive 131I therapy on week 9.

Patients are followed at 3 and 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed papillary thyroid or follicular thyroid carcinoma:

    • Differentiated disease;

      • Metastatic disease documented by ultrasound, computed tomography (CT) scan (without iodinated contrast), or MRI - All metastatic disease foci =< 10 mm in all dimensions
  • Must have been treated with total or near-total thyroidectomy AND at least 1 course of iodine I 131 (131I)(>=29.9 mCi) OR demonstrated negative uptake on a postoperative low-dose131I scan
  • Must have undergone whole body 131I scan 1-3 days after administration of =< 5.5 mCi of 131I demonstrating no visible iodine uptake within the lesions unless demonstrated negative uptake on a postoperative low-dose131I scan within the past 12 weeks:

    • Must have 24-hour urine iodine excretion =< 500 mcg within 1 week of 131I scan
  • Must be receiving thyroid hormone therapy AND have thyroid-stimulating hormone level =< 0.5 mU/L
  • No known brain metastases
  • Performance status:

    • Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100%
  • Hematopoietic:

    • Absolute neutrophil count >= 1,500/mm3;
    • Platelet count >= 100,000/mm3;
    • White Blood Count (WBC) >= 3,000/mm3
  • Hepatic:

    • aspartate aminotransferase-alanine aminotransferase (AST and ALT) =< 2.5 times upper limit of normal;
    • Bilirubin normal
  • Renal:

    • Creatinine not elevated OR
    • Creatinine clearance >= 60 mL/min
  • Cardiovascular:

    • No symptomatic congestive heart failure;
    • No unstable angina pectoris;
    • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to decitabine
  • No concurrent uncontrolled illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No prior cytotoxic chemotherapy for thyroid cancer
  • At least 6 months since prior external beam radiotherapy administered for locoregional disease in the thyroid bed or to the cervical or upper mediastinal lymph node regions (no more than 6,000 cGy)
  • More than 6 months since other prior radiotherapy and recovered
  • More than 6 months since prior therapeutic 131I > 10 mCi
  • More than 18 months since prior cumulative 131I activity of at least 500 mCi
  • More than 12 months since prior amiodarone (Unless 24-hour urinary iodine excretion is =< 500 mcg)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  • More than 6 months since prior intrathecal iodinated contrast (Unless 24-hour urinary iodine excretion is =< 500 mcg)
  • More than 3 months since prior IV or oral iodinated contrast for radiographic studies (Unless 24-hour urinary iodine excretion is =< 500 mcg)
  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: NCT00085293

Locations
United States, Colorado
University of Colorado at Denver
Aurora, Colorado, United States, 80045
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Sherman M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00085293     History of Changes
Other Study ID Numbers: NCI-2009-00033, NCI-2009-00033, CDR0000368467, 5954, 2003-0308, 5954, P30CA016672, N01CM62207
Study First Received: June 10, 2004
Results First Received: August 20, 2014
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma
Adenocarcinoma, Follicular
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Iodine
Decitabine
Fluorodeoxyglucose F18
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Radiopharmaceuticals
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on September 18, 2014