Trial Outcomes & Findings for Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma (NCT NCT01195922)

NCT ID: NCT01195922

Last Updated: 2017-12-06

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: 21 days post treatment with rapamycin
• Results posted on: 2017-12-06

Participant Flow

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.

37 participants signed consent, 16 participants received study drug.

Participant milestones

Measure	Sirolimus 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.
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma

Baseline characteristics by cohort

Measure	Sirolimus n=16 Participants 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.
Age, Continuous	63 years STANDARD_DEVIATION 11.48 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants

PRIMARY outcome

Timeframe: 21 days post treatment with rapamycin

Population: paraffin embedded formalin fixed tissues including head and neck cancer lesion were not available for 2 participants

Outcome measures

Measure	Sirolimus n=14 Participants 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.
Percent (%) Change in Levels of pS6, pAKt473, and Ki-67 pS6	-60.60 percentage of change from baseline Standard Deviation 18.71
Percent (%) Change in Levels of pS6, pAKt473, and Ki-67 pAKt473	-67.24 percentage of change from baseline Standard Deviation 34.28
Percent (%) Change in Levels of pS6, pAKt473, and Ki-67 Ki-67	-31.48 percentage of change from baseline Standard Deviation 35.47
Percent (%) Change in Levels of pS6, pAKt473, and Ki-67 pERK	100.00 percentage of change from baseline Standard Deviation 104.95

PRIMARY outcome

Timeframe: 21 days post treatment with rapamycin

Population: It was not possible to obtain appropriate CT scans or SUV measurement from all participants

Outcome measures

Measure	Sirolimus n=14 Participants 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.
Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value Tumor size by CT	-15.75 percentage change from baseline Standard Deviation 26.46
Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value SUV non-nodal target lesions	-31.84 percentage change from baseline Standard Deviation 27.90
Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value SUV lymph nodes	-48.01 percentage change from baseline Standard Deviation 23.67

PRIMARY outcome

Timeframe: Percent (%) change from Pre to Post treatement (~21 days)

Population: Same sample loss during processing for phosphor and magnesium

Outcome measures

Measure	Sirolimus n=16 Participants 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.
Percent (%) Change in Clinical and Laboratory Evaluations for Safety ANC	-45.51 percentage change from baseline Standard Deviation 13.456
Percent (%) Change in Clinical and Laboratory Evaluations for Safety HCT	-5.71 percentage change from baseline Standard Deviation 6.141
Percent (%) Change in Clinical and Laboratory Evaluations for Safety HGB	-5.32 percentage change from baseline Standard Deviation 6.747
Percent (%) Change in Clinical and Laboratory Evaluations for Safety MCH	-2.53 percentage change from baseline Standard Deviation 1.328
Percent (%) Change in Clinical and Laboratory Evaluations for Safety MCHC	0.38 percentage change from baseline Standard Deviation 2.090
Percent (%) Change in Clinical and Laboratory Evaluations for Safety MCV	-2.88 percentage change from baseline Standard Deviation 1.399
Percent (%) Change in Clinical and Laboratory Evaluations for Safety MPV	-0.85 percentage change from baseline Standard Deviation 5.149
Percent (%) Change in Clinical and Laboratory Evaluations for Safety PLAT	-25.10 percentage change from baseline Standard Deviation 18.045
Percent (%) Change in Clinical and Laboratory Evaluations for Safety RBC	-2.87 percentage change from baseline Standard Deviation 6.920
Percent (%) Change in Clinical and Laboratory Evaluations for Safety RDW	-5.19 percentage change from baseline Standard Deviation 2.909
Percent (%) Change in Clinical and Laboratory Evaluations for Safety WBC	-32.31 percentage change from baseline Standard Deviation 11.911
Percent (%) Change in Clinical and Laboratory Evaluations for Safety Ca	-4.80 percentage change from baseline Standard Deviation 2.329
Percent (%) Change in Clinical and Laboratory Evaluations for Safety Cl	-0.25 percentage change from baseline Standard Deviation 2.925
Percent (%) Change in Clinical and Laboratory Evaluations for Safety CO2	-1.26 percentage change from baseline Standard Deviation 8.261
Percent (%) Change in Clinical and Laboratory Evaluations for Safety CREATININE	-3.31 percentage change from baseline Standard Deviation 10.397
Percent (%) Change in Clinical and Laboratory Evaluations for Safety GLUCOSE	16.28 percentage change from baseline Standard Deviation 37.433
Percent (%) Change in Clinical and Laboratory Evaluations for Safety K	-3.55 percentage change from baseline Standard Deviation 9.259
Percent (%) Change in Clinical and Laboratory Evaluations for Safety Mg	-4.22 percentage change from baseline Standard Deviation 7.691
Percent (%) Change in Clinical and Laboratory Evaluations for Safety Na	-0.60 percentage change from baseline Standard Deviation 1.933
Percent (%) Change in Clinical and Laboratory Evaluations for Safety PHOSPHOR	-6.58 percentage change from baseline Standard Deviation 16.324
Percent (%) Change in Clinical and Laboratory Evaluations for Safety BUN	-0.00 percentage change from baseline Standard Deviation 32.782

Adverse Events

Sirolimus

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sirolimus n=16 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Injury, procedural complications/post-operative wound complication	6.2% 1/16 • Number of events 1 • Adverse events were collected from the time of consent to one year post treatment. 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.
Infections and infestations Injury, procedural complications/postoperative wound complication	6.2% 1/16 • Number of events 2 • Adverse events were collected from the time of consent to one year post treatment. 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.
Cardiac disorders Cardiac Disorder	6.2% 1/16 • Number of events 1 • Adverse events were collected from the time of consent to one year post treatment. 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.

Other adverse events

Measure	Sirolimus n=16 participants at risk 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.
Blood and lymphatic system disorders Thrombocytopenia	50.0% 8/16 • Number of events 8 • Adverse events were collected from the time of consent to one year post treatment. 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.
Investigations Investigations	43.8% 7/16 • Number of events 7 • Adverse events were collected from the time of consent to one year post treatment. 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.
Gastrointestinal disorders Gastrointestinal disorders	18.8% 3/16 • Number of events 3 • Adverse events were collected from the time of consent to one year post treatment. 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.
Nervous system disorders Nervous system disorders	18.8% 3/16 • Number of events 3 • Adverse events were collected from the time of consent to one year post treatment. 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.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	18.8% 3/16 • Number of events 3 • Adverse events were collected from the time of consent to one year post treatment. 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.
General disorders General Disorders and administration site conditions	12.5% 2/16 • Number of events 2 • Adverse events were collected from the time of consent to one year post treatment. 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.
Injury, poisoning and procedural complications Injury, poisoning, and procedural complications	12.5% 2/16 • Number of events 2 • Adverse events were collected from the time of consent to one year post treatment. 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.
Metabolism and nutrition disorders Metabolism and nutrition disorders	12.5% 2/16 • Number of events 2 • Adverse events were collected from the time of consent to one year post treatment. 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.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	12.5% 2/16 • Number of events 2 • Adverse events were collected from the time of consent to one year post treatment. 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.
Cardiac disorders Cardiac disorders	6.2% 1/16 • Number of events 1 • Adverse events were collected from the time of consent to one year post treatment. 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.

Additional Information

D. J. Silvio Gutkind

University of California San Diego

Phone: (858) 534 5980

Email: sgutkind@ucsd.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place