Intervention: Sirolimus
Trial phase: Phase 1 | Phase 2
ATC code: L01EG04 | L04AA10 | S01XA23
SMILES: COC1CC2CCC(C)C(O)(O2)C(=O)C(=O)N2CCCCC2C(=O)OC(C(C)CC2CCC(O)C(OC)C2)CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C1C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 16
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.
Eligibility criteria:
ELIGIBILITY CRITERIA:

Males and females and members of any race or ethnic group who meet the eligibility criteria may participate in this trial.

INCLUSION CRITERIA:

Participants must meet all of the following inclusion criteria:

Age 18 years and older
Histologically confirmed previously untreated squamous cell carcinoma o f the oral cavity or oropharynx accessible for biopsy
Clinical stage II, III, or IVA disease without distant metastasis, as defined by the American Joint Committee on Cancer Staging System, Seventh edition.
Definitive therapy to include surgical resection or chemoradiation for curative purposes
Life expectancy o f greater than 6 months
Eastern Cooperative Oncology Group ( ECOG) performance status of 0 or 1
Willing and able to provide written informed consent

EXCLUSION CRITERIA:

Participants who meet any of the following criteria are not eligible for enrollment:

Surgical resection or chemoradiation of the HNSCC is contraindicated
Prior head or neck squamous cell carcinoma within 5 years, except for previously treated skin cancer
Received chemotherapy targeted monoclonal antibody therapy or investigational therapy within 30 days prior to enrollment
Previous radiation therapy to the head or neck
No measurable tumor remaining after prior biopsy or negative margins from prior biopsy

Inadequate hematologic, renal or liver function within l4 days prior to the first rapamycin dosing visit, as defined by:

Absolute neutrophil count less than 1.5 times 10 (9)/L
CD4 count < 400 (to account for natural fluctuations in CD4 levels, participants with at least one CD4 count (Bullet) 400 within 14 days prior to dosing will not be excluded)
Platelet count less than 100 times 10(9)/L
Hemoglobin less than l0 g/dL (eligibility level for hemoglobin may be reached by transfusion)
AST, ALT or bilirubin greater than 1.5 times the upper limit of local lab normal values
Total cholesterol level greater than 350 mg/dL
Triglyceride level greater than 400 mg/dL
International Normalized Ratio (INR) greater than 1.5
Serum creatinine greater than 1.5mg/dL
Active hepatitis or HBV or HCV infection
Women who are pregnant or lactating (female of child-bearing age must be abstinent or use a barrier type birth control method throughout the study)
Presence of any contraindications to rapamycin therapy, including HlV-protease inhibitors and drugs or agents that are modulators of cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein(P-gp)
Hypersensitivity to rapamycin

11 .Has received live vaccine (such as influenza nasal vaccine measles mumps, rubella, oral polio, B CG, yellow fever, varicella, or TY2la typhoid) in the past 30 days or has plans to take a live vaccine in the next 3 months

12. Any cognitive impairment that limits the subject s or the subject s legally authorized representative s ability to understand the protocol, provide informed consent or assent, or to comply with the protocol procedures

13.Unable or unwilling to comply with the requirements of the protocol