Clinical trial NCT00085293: Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131
Official title: Phase II Study of Decitabine in Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Radioiodine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-06-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration
timeFrame: Week 3 following 2 weeks of Decitabine therapy
Secondary outcomes:
measure: Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
timeFrame: Up to 6 months
measure: Efficacy of Subsequent Radioiodine Therapy in Terms of CR/PR/SD of Any Radiographic Disease.
timeFrame: 6 months
measure: Change in Fludeoxyglucose (FDG) Uptake Measured by Positron Emission Tomography in Metastatic Tumor Sites Before and After DNA-methyltransferase Inhibitor Therapy (Optional). No Secondary Endpoints Were Measured as no Patient Met the Primary Endpoint.
timeFrame: Baseline to 3 weeks
measure: Efficacy of Subsequent Radioiodine Therapy in Terms of Complete Response (CR)/Partial Response (PR)/Stable Disease (SD) of Any Radiographic Disease
timeFrame: 3 months
measure: Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level
timeFrame: 6 months
measure: Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level.These Secondary Endpoints Would Only Have Been Assessed if a Patient Had Met the Primary Endpoint, Restoration of Radioiodine Uptake to Justify Radioiodine Therapy.
timeFrame: 3 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado at Denver
state: Colorado
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Steven Sherman
role: PRINCIPAL_INVESTIGATOR
References: