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Trial record 65 of 146 for:    epilepsy AND Bethesda

A Phase II Trial of Valproic Acid in Patients With Advanced Thyroid Cancers of Follicular Cell Origin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01182285
Recruitment Status : Completed
First Posted : August 16, 2010
Results First Posted : December 14, 2016
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Naris Nilubol, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Thyroid Neoplasm
Interventions Drug: Valproic Acid
Drug: Liothyronine Sodium
Enrollment 13
Recruitment Details  
Pre-assignment Details Five and eight participants were enrolled from University of California San Francisco (UCSF) and the National Institutes of Health (NIH), respectively.
Arm/Group Title A - Phase 1 Radioiodine Resistant Thyroid Cancer B1 - Phase 2 Schedule 1 (Increased Radioiodine Uptake) B2 - Phase 2 Schedule 2 (No Increased Radioiodine Uptake)
Hide Arm/Group Description Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Drug: Valproic Acid Week 11 - 17 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Drug: Cytomel (25 micrograms) Patients who exhibit an increased radioiodine uptake on Thyrogen scan post valproic acid therapy at week 10. Begin Liothyronine Sodium (Cytomel) for 4 weeks (25 micrograms twice a day) Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.
Period Title: First Intervention Week 1-10
Started 13 0 0
Completed 10 0 0
Not Completed 3 0 0
Reason Not Completed
Disease progression             1             0             0
Adverse Event             1             0             0
Non-compliance             1             0             0
Period Title: Second Intervention Week 11-17
Started 0 0 0
Completed 0 0 0
Not Completed 0 0 0
Period Title: Third Intervention Week 11-52
Started 0 0 8 [1]
Completed 0 0 0
Not Completed 0 0 8
Reason Not Completed
Disease Progression             0             0             6
Other             0             0             2
[1]
2 subj. taken off study after completing ph 1: 1 due to a negative uptake scan & one off due to PD.
Arm/Group Title All Participants (Phase 1 and Phase 2 Schedule 2)
Hide Arm/Group Description

A- Phase 1 Radioiodine-Resistant Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening

B2 - Phase 2 Schedule 2 Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.

Overall Number of Baseline Participants 13
Hide Baseline Analysis Population Description
Five and eight participants were enrolled from University of California San Francisco (UCSF), and the National Institutes of Health, respectively.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
<=18 years
0
   0.0%
Between 18 and 65 years
9
  69.2%
>=65 years
4
  30.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants
61.08  (7.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Female
4
  30.8%
Male
9
  69.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
11
  84.6%
Unknown or Not Reported
2
  15.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  15.4%
White
9
  69.2%
More than one race
0
   0.0%
Unknown or Not Reported
2
  15.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 13 participants
13
 100.0%
1.Primary Outcome
Title RAI (Radioactive Iodine) Uptake and Tg (Thyroglobulin) Level Compared Pre and Post- Valproic Treatment
Hide Description Complete response (CR) is increased Rai uptake on post- valproic acid therapy at week 10, AND a decrease in Tg level to less than 2 ng/ml (or a decrease in Tg-Ab level to less than 2.0 IU/ml) at 10 weeks AND disappearance of all lesions at 16 weeks. Partial response (PR) is increased Rai uptake on post-valproic scan at week 10, OR a decreased Tg level (or a decrease in Tg Ab (Tg antibody) level by more than 20%) at 10 weeks AND 30% decrease in target lesion at 16 weeks. Stable disease (SD) is no change in RAI uptake AND Tg levels (or TG-Ab level) AND no significant change of lesions at 16 weeks. Progressive disease (PD) is tumor mass increases OR Tg levels (or Tg-Ab levels) increases over 10 weeks OR at least 20% increase in target lesion at 16 weeks.
Time Frame Entry to study and after 10 weeks of treatment for Phase 1, and 10 weeks of treatment to 16 weeks of treatment for phase 2.
Hide Outcome Measure Data
Hide Analysis Population Description
13 participants were enrolled in phase 1 and 8/13 (5 from University of California San Francisco (UCSF) moved on from phase 1 to the phase 2 schedule 2 portion. However, Tg data from UCSF is unavailable for 5 of the participant, thus only 3 were analyzed in the phase 2 portion.
Arm/Group Title A - Phase 1 Radioiodine Resistant Thyroid Cancer B2 - Phase 2 Schedule 2 (No Increased Radioiodine Uptake)
Hide Arm/Group Description:
Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening
Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.
Overall Number of Participants Analyzed 13 3
Measure Type: Count of Participants
Unit of Measure: Participants
Tg start - >900 ng/ml
6
  46.2%
1
  33.3%
Tg start - 707 ng/ml
1
   7.7%
0
   0.0%
Tg start - 661 ng/ml
1
   7.7%
0
   0.0%
Tg start - 362 ng/ml
0
   0.0%
1
  33.3%
Tg start - 289 ng/ml
1
   7.7%
0
   0.0%
Tg start - 183 ng/ml
0
   0.0%
1
  33.3%
Tg start - 154 ng/ml
1
   7.7%
0
   0.0%
Tg start - 101 ng/ml
1
   7.7%
0
   0.0%
Tg start - 99 ng/ml
1
   7.7%
0
   0.0%
Tg start - 15.7 ng/ml
1
   7.7%
0
   0.0%
antiTg start - 142 IU/ml
1
   7.7%
0
   0.0%
antiTg start - 220 IU/ml
0
   0.0%
1
  33.3%
antiTg start - <20 IU/ml
7
  53.8%
2
  66.7%
Tg end - >900 ng/ml
4
  30.8%
1
  33.3%
Tg end - 749 ng/ml
1
   7.7%
0
   0.0%
Tg end - 702 ng/ml
1
   7.7%
0
   0.0%
Tg end - 630 ng/ml
1
   7.7%
0
   0.0%
Tg end - 480 ng/ml
1
   7.7%
1
  33.3%
Tg end - 362 ng/ml
0
   0.0%
0
   0.0%
Tg end - 204 ng/ml
1
   7.7%
0
   0.0%
Tg end - 184 ng/ml
0
   0.0%
1
  33.3%
Tg end - 183 ng/ml
0
   0.0%
0
   0.0%
Tg end - 128 ng/ml
1
   7.7%
0
   0.0%
Tg end - 61 ng/ml
1
   7.7%
0
   0.0%
Tg end - 10.8 ng/ml
1
   7.7%
0
   0.0%
Tg end - none
1
   7.7%
0
   0.0%
antiTg end - 338 IU/ml
1
   7.7%
0
   0.0%
anti Tg end - 220 IU/ml
0
   0.0%
0
   0.0%
antiTg end - 83 IU/ml
1
   7.7%
0
   0.0%
antiTg end - 80 IU/ml
0
   0.0%
1
  33.3%
anti Tg end - <20 IU/ml
5
  38.5%
2
  66.7%
antiTg end - none
1
   7.7%
0
   0.0%
RAI uptake pre-treatment - none
13
 100.0%
0
   0.0%
RAI uptake post treatment - none
10
  76.9%
0
   0.0%
2.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame Date treatment consent signed to date off study, approximately 41 months and 11 days
Hide Outcome Measure Data
Hide Analysis Population Description
Adverse events are not reported per Arm. All adverse events were reported to include phases 1 and 2 since it is analyzed throughout the whole study.
Arm/Group Title All Participants
Hide Arm/Group Description:
A - Phase 1 Radioiodine Resistant Thyroid Cancer Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening B2 - Phase 2 Schedule 2 (No Increased Radioiodine Uptake) Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
8
  61.5%
3.Secondary Outcome
Title Best Overall Response
Hide Description Best overall response was assessed by radioiodine uptake. Complete response (CR) is increased Rai (radioiodine) uptake on post- valproic acid therapy at week 10, AND a decrease in Tg (thyroglobulin ) level to less than 2 ng/ml (or a decrease in Tg-Ab (thyroglobulin antibodies) level to less than 2.0 IU/ml) at 10 weeks AND disappearance of all lesions at 16 weeks. Partial response (PR) is increased Rai uptake on post-valproic scan at week 10, OR a decreased Tg level (or a decrease in Tg Ab (Tg antibody) level by more than 20%) at 10 weeks AND 30% decrease in target lesion at 16 weeks. Stable disease (SD) is no change in RAI uptake AND Tg levels (or TG-Ab level) AND no significant change of lesions at 16 weeks. Progressive disease (PD) is tumor mass increases OR Tg levels (or Tg-Ab levels) increases over 10 weeks OR at least 20% increase in target lesion at 16 weeks.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Best overall response was not assessed for the phase 1 portion.
Arm/Group Title B2 - Phase 2 Schedule 2 (No Increased Radiiodine Uptake)
Hide Arm/Group Description:
Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.
Overall Number of Participants Analyzed 8
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
0
   0.0%
Partial Response (PR)
0
   0.0%
Stable Disease (SD)
1
  12.5%
Progressive Disease (PD)
6
  75.0%
Unknown
1
  12.5%
4.Secondary Outcome
Title NIS (Na/I-symporter) Expression
Hide Description NIS (Na/I-symporter) Expression is assessed by quantitative reverse transcription (RT) polymerase chain reaction (PCR) and immunohistochemistry (IHC). NIS mRNA expression was measured by quantitative RT PCR from biopsy samples.
Time Frame Entry to study and after 10 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
There is no standard of error to report. The acronym GAPDH expanded is glyceraldehyde 3-phosphate dehydrogenase. Only 1 participant was analyzed because biopsies were not performed in 12 subjects.
Arm/Group Title A - Phase 1 Radioiodine Resistant Thyroid Cancer
Hide Arm/Group Description:
Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening
Overall Number of Participants Analyzed 1
Median (Standard Error)
Unit of Measure: percent expression
Pre-treatment NIS expression (relative to GAPDH) 21  (0)
Post-treatment NIS expression (relative to GAPDH) 25  (0)
Time Frame Date treatment consent signed to date off study, approximately 41 months and 11 days
Adverse Event Reporting Description Adverse events are not reported per Arm. All adverse events were reported to include phases 1 and 2 since it is analyzed throughout the whole study. No adverse events were recorded for participants at University of California San Francisco (UCSF).
 
Arm/Group Title All Participants (Phase 1 and Phase 2 Schedule 2)
Hide Arm/Group Description A - Phase 1 Radioiodine Resistant Thyroid Cancer Drug: Valproic Acid Week 1 - 10 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening B2 - Phase 2 Schedule 2 (No Increased Radioiodine Uptake) Drug: Valproic Acid Week 11 - 52 (Days 1-3): Valproic acid - 500 mg every evening (Day 4-7): Valproic acid - 500 mg twice daily (morning and evening) Weeks 2 through 10: Valproic acid 500 mg every morning and 1000 mg every evening Weeks 17-52: Patients who show a response by RECIST criteria or have a decreased thyroglobulin level from Day 1 of the treatment (registered as a partial response to the treatment) will continue on valproic acid at their current dose for a total of 52 weeks.
All-Cause Mortality
All Participants (Phase 1 and Phase 2 Schedule 2)
Affected / at Risk (%)
Total   0/13 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
All Participants (Phase 1 and Phase 2 Schedule 2)
Affected / at Risk (%) # Events
Total   2/13 (15.38%)    
Psychiatric disorders   
Confusion  1  1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/13 (7.69%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Participants (Phase 1 and Phase 2 Schedule 2)
Affected / at Risk (%) # Events
Total   8/13 (61.54%)    
Blood and lymphatic system disorders   
Anemia  1  5/13 (38.46%)  7
Eye disorders   
Diarrhea  1  1/13 (7.69%)  1
Gastrointestinal disorders   
Dyspepsia  1  1/13 (7.69%)  1
General disorders   
Fatigue  1  2/13 (15.38%)  2
Fever  1  1/13 (7.69%)  1
Investigations   
Alanine aminotransferase increased  1  1/13 (7.69%)  1
Alkaline phosphatase increased  1  1/13 (7.69%)  1
Aspartate aminotransferase increased  1  1/13 (7.69%)  1
Creatinine increased  1  1/13 (7.69%)  1
Lymphocyte count decreased  1  5/13 (38.46%)  8
Platelet count decreased  1  3/13 (23.08%)  3
Serum amylase increased  1  1/13 (7.69%)  1
White blood cell decreased  1  1/13 (7.69%)  2
Metabolism and nutrition disorders   
Hypercalcemia  1  1/13 (7.69%)  3
Hyperglycemia  1  1/13 (7.69%)  1
Hypermagnesemia  1  1/13 (7.69%)  1
Hypoalbuminemia  1  3/13 (23.08%)  4
Hyponatremia  1  1/13 (7.69%)  2
Musculoskeletal and connective tissue disorders   
Generalized muscle weakness  1  1/13 (7.69%)  1
Psychiatric disorders   
Insomnia  1  1/13 (7.69%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/13 (15.38%)  2
Hypoxia  1  2/13 (15.38%)  2
Pleural effusion  1  1/13 (7.69%)  1
Skin and subcutaneous tissue disorders   
Alopecia  1  1/13 (7.69%)  1
Vascular disorders   
Hypertension  1  1/13 (7.69%)  2
Hypotension  1  1/13 (7.69%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Naris Nilubol
Organization: National Cancer Institute
Phone: 301-451-2355
EMail: niluboln@nih.gov
Layout table for additonal information
Responsible Party: Naris Nilubol, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01182285     History of Changes
Other Study ID Numbers: 100041
10-C-0041
First Submitted: August 13, 2010
First Posted: August 16, 2010
Results First Submitted: August 22, 2016
Results First Posted: December 14, 2016
Last Update Posted: May 16, 2018