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

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:	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:

MedlinePlus related topics: Thyroid Cancer Thyroid Diseases

Drug Information available for: Decitabine Iodine Thyroid

Genetic and Rare Diseases Information Center resources: Thyroid Cancer, Follicular Papillary Thyroid Carcinoma

U.S. FDA Resources

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 ]
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 ]
Efficacy of Subsequent Radioiodine Therapy in Terms of Change in Serum Thyroglobulin Level [ Time Frame: 6 months ]
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 ]
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 ]
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 ]
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 ]
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

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 (Adult, Senior)
Sexes Eligible for Study:	All
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Steven Sherman	M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Official Website This link exits the ClinicalTrials.gov site


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00085293 History of Changes
Other Study ID Numbers:	NCI-2009-00033 NCI-2009-00033 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000368467 5954 2003-0308 ( Other Identifier: M D Anderson Cancer Center ) 5954 ( Other Identifier: CTEP ) P30CA016672 ( US NIH Grant/Contract Award Number ) N01CM62207 ( US NIH Grant/Contract Award Number )
Study First Received:	June 10, 2004
Results First Received:	August 20, 2014
Last Updated:	August 20, 2014

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 Decitabine Azacitidine Iodine	Cadexomer iodine Fluorodeoxyglucose F18 Calcitonin Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors Anti-Infective Agents, Local Anti-Infective Agents Trace Elements Micronutrients Growth Substances Physiological Effects of Drugs Radiopharmaceuticals

ClinicalTrials.gov processed this record on June 26, 2017