Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131
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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 |
- 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.
- 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:
Radiation: Iodine I 131
Undergo thyrotropin-alfa stimulated radioactive iodine scan
Other Names:
Biological: Recombinant thyrotropin alfa
Undergo thyrotropin-alfa stimulated radioactive iodine scan
Other Name: Thyrogen
Radiation: Fludeoxyglucose F 18
Optional correlative studies
Other Names:
Procedure: Positron emission tomography
Optional correlative studies
Other Names:
|
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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00085293
| 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 | |
| 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:
|
Adenocarcinoma, Follicular Carcinoma Thyroid Diseases Thyroid Neoplasms Adenocarcinoma Endocrine Gland Neoplasms Endocrine System Diseases Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Decitabine Iodine |
Anti-Infective Agents Anti-Infective Agents, Local Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Enzyme Inhibitors Growth Substances Micronutrients Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses Trace Elements |
ClinicalTrials.gov processed this record on February 27, 2015