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Combination of Temsirolimus and Sorafenib in the Treatment of Radioactive Iodine Refractory Thyroid Cancer

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ClinicalTrials.gov Identifier: NCT01025453
Recruitment Status : Completed
First Posted : December 3, 2009
Results First Posted : August 15, 2018
Last Update Posted : August 15, 2018
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Pfizer
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Thyroid Cancer
Intervention Drug: Temsirolimus and Sorafenib
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Period Title: Overall Study
Started 37
Completed 37
Not Completed 0
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
64
(30 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
17
  45.9%
Male
20
  54.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Hispanic or Latino
3
   8.1%
Not Hispanic or Latino
34
  91.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   8.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
6
  16.2%
White
25
  67.6%
More than one race
0
   0.0%
Unknown or Not Reported
3
   8.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 37 participants
37
 100.0%
1.Primary Outcome
Title Reponse Rate of the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 participants were not evaluable because they came off treatment before the first radiographic scan for reasons other than progression of disease, including but not limited to excessive toxicity (n=1), withdrawal of consent (n=3), and seeing other treatment (n=1).
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description:
We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Partial Response
8
  26.7%
Stable Disease
21
  70.0%
Disease Progression
1
   3.3%
2.Secondary Outcome
Title Duration of Study Treatment for Participants With and Without BRAF Mutations
Hide Description [Not Specified]
Time Frame 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis separated the participants into 2 groups (number of patients with BRAF V600E Mutation and number of patients without BRAF V600E Mutation)
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description:
We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Overall Number of Participants Analyzed 36
Median (Full Range)
Unit of Measure: months
Pts with BRAF V600E Mutation Number Analyzed 10 participants
5.2
(0.7 to 63)
Pts w/o BRAF V600E Mutation Number Analyzed 26 participants
6.7
(0.5 to 25.6)
3.Secondary Outcome
Title Percentage of Participants With Progression-free Survival Under the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Hide Description Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description:
We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: percentage of patients
30.5
4.Secondary Outcome
Title Safety and Tolerability for the Combination Sorafenib and Temsirolimus in I-131 Refractory Thyroid Cancer.
Hide Description Participant toxicities evaluated by CTCAE version 4.0
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description:
We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
37
 100.0%
Time Frame 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Pts Getting Temsirolimus and Sorafenib
Hide Arm/Group Description We propose a phase II study to evaluate the efficacy of the combination sorafenib with temsirolimus in patients with thyroid cancer of follicular cell origin (e.g., papillary, follicular, Hurthle cell). A maximum of 36 subjects will be evaluated during the study. Restaging scans, with evaluation of response, will be done every 2 cycles (8 weeks of treatment). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay > 4 weeks, or at the discretion of the treating physician or patient.
All-Cause Mortality
Pts Getting Temsirolimus and Sorafenib
Affected / at Risk (%)
Total   32/37 (86.49%) 
Show Serious Adverse Events Hide Serious Adverse Events
Pts Getting Temsirolimus and Sorafenib
Affected / at Risk (%)
Total   23/37 (62.16%) 
Blood and lymphatic system disorders   
Anemia   4/37 (10.81%) 
Cardiac disorders   
Chest pain - cardiac   1/37 (2.70%) 
Heart failure   1/37 (2.70%) 
Sinus tachycardia   2/37 (5.41%) 
Gastrointestinal disorders   
Abdominal Pain   3/37 (8.11%) 
Colonic perforation   2/37 (5.41%) 
Constipation   1/37 (2.70%) 
Diarrhea   3/37 (8.11%) 
Dysphagia   2/37 (5.41%) 
Mucositis oral   1/37 (2.70%) 
Nausea   4/37 (10.81%) 
Oral pain   1/37 (2.70%) 
Small intestinal obstruction   1/37 (2.70%) 
Vomiting   7/37 (18.92%) 
General disorders   
Cough   1/37 (2.70%) 
Death NOS   2/37 (5.41%) 
Edema limbs   2/37 (5.41%) 
Fatigue   2/37 (5.41%) 
Fever   3/37 (8.11%) 
Non-cardiac chest pain   3/37 (8.11%) 
Pain   1/37 (2.70%) 
Sudden death NOS   1/37 (2.70%) 
Infections and infestations   
Appendicitis   1/37 (2.70%) 
Catheter related infection   2/37 (5.41%) 
Infections and infestations - Other, specify   1/37 (2.70%) 
Lung infection   2/37 (5.41%) 
Urinary tract infection   1/37 (2.70%) 
Wound infection   1/37 (2.70%) 
Injury, poisoning and procedural complications   
Spinal fracture   1/37 (2.70%) 
Investigations   
Alanine aminotransferase increased   1/37 (2.70%) 
Aspartate aminotransferase increased   1/37 (2.70%) 
Creatinine increased   1/37 (2.70%) 
Lymphocyte count decreased   1/37 (2.70%) 
Platelet count decreased   1/37 (2.70%) 
Metabolism and nutrition disorders   
Anorexia   1/37 (2.70%) 
Dehydration   3/37 (8.11%) 
Hyperkalemia   2/37 (5.41%) 
Hypokalemia   1/37 (2.70%) 
Musculoskeletal and connective tissue disorders   
Back pain   3/37 (8.11%) 
Neck pain   1/37 (2.70%) 
Nervous system disorders   
Dizziness   2/37 (5.41%) 
Dysarthria   2/37 (5.41%) 
Headache   1/37 (2.70%) 
Paresthesia   1/37 (2.70%) 
Seizure   1/37 (2.70%) 
Psychiatric disorders   
Confusion   1/37 (2.70%) 
Delirium   1/37 (2.70%) 
Renal and urinary disorders   
Urinary retention   2/37 (5.41%) 
Reproductive system and breast disorders   
Vaginal hemorrhage   1/37 (2.70%) 
Respiratory, thoracic and mediastinal disorders   
Aspiration   1/37 (2.70%) 
Bronchopulmonary hemorrhage   5/37 (13.51%) 
Dyspnea   6/37 (16.22%) 
Hypoxia   1/37 (2.70%) 
Laryngeal hemorrhage   2/37 (5.41%) 
Mediastinal hemorrhage   1/37 (2.70%) 
Pleural effusion   2/37 (5.41%) 
Pneumonitis   1/37 (2.70%) 
Respiratory failure   1/37 (2.70%) 
Skin and subcutaneous tissue disorders   
Skin ulceration   1/37 (2.70%) 
Vascular disorders   
Hypertension   3/37 (8.11%) 
Hypotension   3/37 (8.11%) 
Thromboembolic event   2/37 (5.41%) 
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 5%
Pts Getting Temsirolimus and Sorafenib
Affected / at Risk (%)
Total   37/37 (100.00%) 
Blood and lymphatic system disorders   
Anemia   7/37 (18.92%) 
Cardiac disorders   
Sinus tachycardia   2/37 (5.41%) 
Gastrointestinal disorders   
Diarrhea   11/37 (29.73%) 
Nausea   3/37 (8.11%) 
Mucositis oral   7/37 (18.92%) 
Vomiting   3/37 (8.11%) 
Dysphagia   5/37 (13.51%) 
Abdominal pain   3/37 (8.11%) 
Oral pain   2/37 (5.41%) 
Colonic perforation   2/37 (5.41%) 
General disorders   
Fatigue   14/37 (37.84%) 
Edema limbs   4/37 (10.81%) 
Fever   2/37 (5.41%) 
Non-cardiac chest pain   2/37 (5.41%) 
Investigations   
Platelet count decreased   11/37 (29.73%) 
Aspartate aminotransferase increased   6/37 (16.22%) 
Alanine aminotransferase increased   8/37 (21.62%) 
Weight loss   7/37 (18.92%) 
White blood cell decreased   5/37 (13.51%) 
Creatinine increased   2/37 (5.41%) 
Metabolism and nutrition disorders   
Hyperglycemia   21/37 (56.76%) 
Hypertriglyceridemia   6/37 (16.22%) 
Anorexia   12/37 (32.43%) 
Dehydration   2/37 (5.41%) 
Musculoskeletal and connective tissue disorders   
Back pain   3/37 (8.11%) 
Myalgia   2/37 (5.41%) 
Nervous system disorders   
Dysgeusia   3/37 (8.11%) 
Headache   4/37 (10.81%) 
Dizziness   2/37 (5.41%) 
Respiratory, thoracic and mediastinal disorders   
Cough   3/37 (8.11%) 
Dyspnea   5/37 (13.51%) 
Pleural effusion   3/37 (8.11%) 
Skin and subcutaneous tissue disorders   
Rash maculo-papular   6/37 (16.22%) 
Palmar-plantar erythrodysesthesia syndrome   6/37 (16.22%) 
Rash acneiform   2/37 (5.41%) 
Vascular disorders   
Hypertension   15/37 (40.54%) 
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Eric Sherman, MD
Organization: Memorial Sloan Kettering Cancer Center
Phone: 646-888-4234
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01025453     History of Changes
Other Study ID Numbers: 09-148
First Submitted: December 2, 2009
First Posted: December 3, 2009
Results First Submitted: April 2, 2018
Results First Posted: August 15, 2018
Last Update Posted: August 15, 2018