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Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT01195922
Recruitment Status : Completed
First Posted : September 6, 2010
Results First Posted : January 19, 2017
Last Update Posted : December 6, 2017
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Mouth Neoplasms
Head and Neck Neoplasms
Tongue Neoplasms
Carcinoma, Squamous Cell
Intervention Drug: Sirolimus
Enrollment 37
Recruitment Details Subjects were recruited from the National Institute of Health (NIH) as well as the Medical University of South Carolina (MUSC). Recruitment began 5/16/2011 with a total of 37 subjects consented; 34 at MUSC and 3 and NIH. Of the 37 consented, 16 subjects received study intervention and completed the study.
Pre-assignment Details 37 participants signed consent, 16 participants received study drug.
Arm/Group Title Sirolimus
Hide Arm/Group Description Rapamycin (sirolimus), dispensed as either tablets or an oral solution for patients with dysphagia was administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Dose reductions to 3 mg by mouth once per day were implemented if levels of rapamycin > 20 ng/ml occurred on Days 8 or 15.
Period Title: Overall Study
Started 16
Completed 16
Not Completed 0
Arm/Group Title Sirolimus
Hide Arm/Group Description Rapamycin (sirolimus), which will be dispensed as either tablets or an oral solution for patients with dysphagia (see Section 0), will be administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Serum rapamycin levels will be obtained on Days 8, 15, 22, and 28 (if rapamycin is > 3 ng/ml at Day 28, the subject will return daily, or as is convenient, for testing until rapamycin is ≤ 3 ng/ml). Dose reduction to 3 mg by mouth once per day will occur if trough levels of rapamycin > 20 ng/ml occur on Days 8 or 15 (see Appendix A, Study Calendar for visit windows). If a dose is decreased at Day 8, it will not be increased at Day 15 regardless of serum rapamycin levels. If subjects receiving 3 mg have levels > 20 ng/ml at Day 15, rapamycin will be reduced to 2 mg once per day. Rapamycin will cease on Day 21 regardless of level.
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
63  (11.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
0
   0.0%
Male
16
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 16 participants
16
1.Primary Outcome
Title Percent (%) Change in Levels of pS6, pAKt473, and Ki-67
Hide Description [Not Specified]
Time Frame 21 days post treatment with rapamycin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
paraffin embedded formalin fixed tissues including head and neck cancer lesion were not available for 2 participants
Arm/Group Title Sirolimus
Hide Arm/Group Description:
Rapamycin (sirolimus), which will be dispensed as either tablets or an oral solution for patients with dysphagia (see Section 0), will be administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Serum rapamycin levels will be obtained on Days 8, 15, 22, and 28 (if rapamycin is > 3 ng/ml at Day 28, the subject will return daily, or as is convenient, for testing until rapamycin is ≤ 3 ng/ml). Dose reduction to 3 mg by mouth once per day will occur if trough levels of rapamycin > 20 ng/ml occur on Days 8 or 15 (see Appendix A, Study Calendar for visit windows). If a dose is decreased at Day 8, it will not be increased at Day 15 regardless of serum rapamycin levels. If subjects receiving 3 mg have levels > 20 ng/ml at Day 15, rapamycin will be reduced to 2 mg once per day. Rapamycin will cease on Day 21 regardless of level.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percentage of change from baseline
pS6 -60.60  (18.71)
pAKt473 -67.24  (34.28)
Ki-67 -31.48  (35.47)
pERK 100.00  (104.95)
2.Primary Outcome
Title Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value
Hide Description [Not Specified]
Time Frame 21 days post treatment with rapamycin
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
It was not possible to obtain appropriate CT scans or SUV measurement from all participants
Arm/Group Title Sirolimus
Hide Arm/Group Description:
Rapamycin (sirolimus), which will be dispensed as either tablets or an oral solution for patients with dysphagia (see Section 0), will be administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Serum rapamycin levels will be obtained on Days 8, 15, 22, and 28 (if rapamycin is > 3 ng/ml at Day 28, the subject will return daily, or as is convenient, for testing until rapamycin is ≤ 3 ng/ml). Dose reduction to 3 mg by mouth once per day will occur if trough levels of rapamycin > 20 ng/ml occur on Days 8 or 15 (see Appendix A, Study Calendar for visit windows). If a dose is decreased at Day 8, it will not be increased at Day 15 regardless of serum rapamycin levels. If subjects receiving 3 mg have levels > 20 ng/ml at Day 15, rapamycin will be reduced to 2 mg once per day. Rapamycin will cease on Day 21 regardless of level.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Tumor size by CT Number Analyzed 14 participants
-15.75  (26.46)
SUV non-nodal target lesions Number Analyzed 12 participants
-31.84  (27.90)
SUV lymph nodes Number Analyzed 11 participants
-48.01  (23.67)
3.Primary Outcome
Title Percent (%) Change in Clinical and Laboratory Evaluations for Safety
Hide Description [Not Specified]
Time Frame Percent (%) change from Pre to Post treatement (~21 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Same sample loss during processing for phosphor and magnesium
Arm/Group Title Sirolimus
Hide Arm/Group Description:
Rapamycin (sirolimus), which will be dispensed as either tablets or an oral solution for patients with dysphagia (see Section 0), will be administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Serum rapamycin levels will be obtained on Days 8, 15, 22, and 28 (if rapamycin is > 3 ng/ml at Day 28, the subject will return daily, or as is convenient, for testing until rapamycin is ≤ 3 ng/ml). Dose reduction to 3 mg by mouth once per day will occur if trough levels of rapamycin > 20 ng/ml occur on Days 8 or 15 (see Appendix A, Study Calendar for visit windows). If a dose is decreased at Day 8, it will not be increased at Day 15 regardless of serum rapamycin levels. If subjects receiving 3 mg have levels > 20 ng/ml at Day 15, rapamycin will be reduced to 2 mg once per day. Rapamycin will cease on Day 21 regardless of level.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
ANC Number Analyzed 16 participants
-45.51  (13.456)
HCT Number Analyzed 16 participants
-5.71  (6.141)
HGB Number Analyzed 16 participants
-5.32  (6.747)
MCH Number Analyzed 16 participants
-2.53  (1.328)
MCHC Number Analyzed 16 participants
0.38  (2.090)
MCV Number Analyzed 16 participants
-2.88  (1.399)
MPV Number Analyzed 16 participants
-0.85  (5.149)
PLAT Number Analyzed 16 participants
-25.10  (18.045)
RBC Number Analyzed 16 participants
-2.87  (6.920)
RDW Number Analyzed 16 participants
-5.19  (2.909)
WBC Number Analyzed 16 participants
-32.31  (11.911)
BUN Number Analyzed 16 participants
-0.00  (32.782)
Ca Number Analyzed 16 participants
-4.80  (2.329)
Cl Number Analyzed 16 participants
-0.25  (2.925)
CO2 Number Analyzed 16 participants
-1.26  (8.261)
CREATININE Number Analyzed 16 participants
-3.31  (10.397)
GLUCOSE Number Analyzed 16 participants
16.28  (37.433)
K Number Analyzed 16 participants
-3.55  (9.259)
Mg Number Analyzed 15 participants
-4.22  (7.691)
Na Number Analyzed 16 participants
-0.60  (1.933)
PHOSPHOR Number Analyzed 14 participants
-6.58  (16.324)
Time Frame Adverse events were collected from the time of consent to one year post treatment.
Adverse Event Reporting Description Subjects were followed 360 days after treatment, surgical or chemo radiation, to assess survival, recurrence of disease, metastases and adverse events that were related to rapamycin therapy including complications of wound healing, infections due to immune compromise and late radiation toxicities.
 
Arm/Group Title Sirolimus
Hide Arm/Group Description Rapamycin (sirolimus), which will be dispensed as either tablets or an oral solution for patients with dysphagia (see Section 0), will be administered orally as a single loading dose of 15 mg on the first day and 5 mg once a day for the next 20 days. Serum rapamycin levels will be obtained on Days 8, 15, 22, and 28 (if rapamycin is > 3 ng/ml at Day 28, the subject will return daily, or as is convenient, for testing until rapamycin is ≤ 3 ng/ml). Dose reduction to 3 mg by mouth once per day will occur if trough levels of rapamycin > 20 ng/ml occur on Days 8 or 15 (see Appendix A, Study Calendar for visit windows). If a dose is decreased at Day 8, it will not be increased at Day 15 regardless of serum rapamycin levels. If subjects receiving 3 mg have levels > 20 ng/ml at Day 15, rapamycin will be reduced to 2 mg once per day. Rapamycin will cease on Day 21 regardless of level.
All-Cause Mortality
Sirolimus
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Sirolimus
Affected / at Risk (%) # Events
Total   3/16 (18.75%)    
Cardiac disorders   
Cardiac Disorder  1 [1]  1/16 (6.25%)  1
Infections and infestations   
Injury, procedural complications/postoperative wound complication  1 [2]  1/16 (6.25%)  2
Respiratory, thoracic and mediastinal disorders   
Injury, procedural complications/post-operative wound complication  1 [3]  1/16 (6.25%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE Version 4.
[1]
Left Bundle Branch Block diagnosed on routine stress test. Subject had left heart catheterization with stent placement.
[2]
Orocutaneous fistula with left leg epidermolysis. Jaw hardware candida infection, surgical flap necrosis/failure.
[3]
Subject had an active bleed from the original tonsillectomy site intraoperative which necessitated extended intubation to postoperative Day 2 when the subject was successfully extubated without further bleeding or complications.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sirolimus
Affected / at Risk (%) # Events
Total   15/16 (93.75%)    
Blood and lymphatic system disorders   
Thrombocytopenia  1 [1]  8/16 (50.00%)  8
Cardiac disorders   
Cardiac disorders  1 [2]  1/16 (6.25%)  1
Gastrointestinal disorders   
Gastrointestinal disorders  1 [3]  3/16 (18.75%)  3
General disorders   
General Disorders and administration site conditions  1 [4]  2/16 (12.50%)  2
Injury, poisoning and procedural complications   
Injury, poisoning, and procedural complications  1 [5]  2/16 (12.50%)  2
Investigations   
Investigations  1 [6]  7/16 (43.75%)  7
Metabolism and nutrition disorders   
Metabolism and nutrition disorders  1 [7]  2/16 (12.50%)  2
Nervous system disorders   
Nervous system disorders  1 [8]  3/16 (18.75%)  3
Respiratory, thoracic and mediastinal disorders   
Respiratory, thoracic and mediastinal disorders  1 [9]  3/16 (18.75%)  3
Skin and subcutaneous tissue disorders   
Skin and subcutaneous tissue disorders  1 [10]  2/16 (12.50%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE Version 4.
[1]
Thrombocytopenia Neutropenia Anemia Leukopenia
[2]
Coronary artery disease
[3]
Combined events reported: vomiting, dysphagia, nausea, oral pain
[4]
Combined: mucosal inflammation, pain, pyrexia
[5]
Combined: postoperative wound complications and post procedural hemorrhage
[6]
Combined decreased: neutrophil count, phosphorous, potassium, white blood cell, platelet. Combined increased: ALT, AST. BUN, glucose, BUN, hepatic enzymes, monocyte count
[7]
Combined: dehydration, hyperglycemia, hypoalbuminaemia
[8]
Combined headache, dizziness, hypogeusia
[9]
Combined: oropharyngeal pain, nasal congestion
[10]
Combined: photosensitivity and rash
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: D. J. Silvio Gutkind
Organization: University of California San Diego
Phone: (858) 534 5980
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier: NCT01195922     History of Changes
Other Study ID Numbers: 100180
10-D-0180 ( Other Identifier: NIHCC )
First Submitted: September 3, 2010
First Posted: September 6, 2010
Results First Submitted: October 27, 2016
Results First Posted: January 19, 2017
Last Update Posted: December 6, 2017