Trial Outcomes & Findings for Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131 (NCT NCT00085293)

Last Updated: 2018-11-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Week 3 following 2 weeks of Decitabine therapy

Results posted on

2018-11-29

Participant Flow

Participants were consented at the University of Texas (UT) MD Anderson Cancer Center between 8/20/2004 and 4/28/2008. The trial was closed to new patient entry on 8/15/2008.

Participant milestones

Participant milestones
Measure	Treatment 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=12 Participants 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
Age, Continuous	53 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 3 following 2 weeks of Decitabine therapy

Population: Per protocol, 1 participant interpreted by local treating investigator as responsive (increased radioiodine uptake on diagnostic scan after therapy), entered second decitabine treatment receiving radioiodine therapeutic dose. Subsequent central review of both scans for formal protocol response interpreted scans as negative for radioiodine uptake.

Outcome measures

Outcome measures
Measure	Treatment n=12 Participants 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
Restoration of Radioiodine Uptake in Metastatic Lesions as Demonstrated by Diagnostic Whole-body Scanning After Decitabine Administration	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment n=12 Participants 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1, Nausea	42 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1, Fatigue	33 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1, Oral Mucositis	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1, Pharyngolaryngeal pain	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1, Decreased white blood cell	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 2, Fatigue	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 2, Decreased white blood cell	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 2, Neutrophil count decreased	16 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 2, Lymphocyte count decreased	16 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3, Decreased white blood cell	42 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3, Neutrophil count decreased	25 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3, Febrile neutropenia	8 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3, Infections	8 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 3, respiratory disorders	8 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 4, Decreased white blood cell	58 percentage of participants
Frequency of Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 5	0 percentage of participants

SECONDARY outcome

Timeframe: 6 months

Population: No secondary endpoints were measured as no patient met the primary endpoint. These secondary endpoints would only have been assessed if a patient had met the primary endpoint, restoration of radioiodine uptake to justify radioiodine therapy.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 3 weeks

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 months

Outcome measures

Outcome data not reported

Adverse Events

Treatment

Serious events: 9 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=12 participants at risk 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
Blood and lymphatic system disorders Febrile neutropenia	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Infections and infestations Infection	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Blood and lymphatic system disorders White blood cell decreased	41.7% 5/12 • Number of events 5 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Blood and lymphatic system disorders Neutrophil count decreased	75.0% 9/12 • Number of events 9 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Respiratory, thoracic and mediastinal disorders Acute Asthma	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hypercalcemia	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.

Other adverse events

Other adverse events
Measure	Treatment n=12 participants at risk 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. 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. Iodine I 131: Undergo thyrotropin-alfa stimulated radioactive iodine scan Recombinant thyrotropin alfa: Undergo thyrotropin-alfa stimulated radioactive iodine scan
General disorders Abdominal pain	8.3% 1/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Alanine aminotransferase increased	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Blood and lymphatic system disorders Anemia	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Gastrointestinal disorders Anorexia	16.7% 2/12 • Number of events 3 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Aspartate aminotransferase increased	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
General disorders Back pain	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
General disorders Chest wall pain	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Gastrointestinal disorders Constipation	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Creatinine increased	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
General disorders Edema limbs	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
General disorders Fatigue	50.0% 6/12 • Number of events 9 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Gastrointestinal disorders Gingival pain	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Nervous system disorders Headache	25.0% 3/12 • Number of events 3 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hyperglycemia	16.7% 2/12 • Number of events 6 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Vascular disorders Hypertension	8.3% 1/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hypoglycemia	8.3% 1/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hypokalemia	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Metabolism and nutrition disorders Hypophosphatemia	16.7% 2/12 • Number of events 3 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Vascular disorders Hypotension	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Blood and lymphatic system disorders Lymph node pain	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Lymphocyte count decreased	16.7% 2/12 • Number of events 4 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Gastrointestinal disorders Mucositis oral	33.3% 4/12 • Number of events 4 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Gastrointestinal disorders Nausea	33.3% 4/12 • Number of events 4 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Neutrophil count decreased	16.7% 2/12 • Number of events 3 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	25.0% 3/12 • Number of events 3 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Infections and infestations Sinusitis	8.3% 1/12 • Number of events 1 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Investigations Weight loss	16.7% 2/12 • Number of events 2 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.
Infections and infestations White blood cell decreased	25.0% 3/12 • Number of events 11 • Routine clinical trial adverse event monitoring during study treatment for one month or up to six months total, depending on whether additional decitabine and radioactive iodine treatment received. Total study period 5/3/04 to 08/15/08.

Additional Information

Steven I. Sherman, MD / Professor

University of Texas MD Anderson Cancer Center

Phone: 713-792-2841

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60