Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma

This study has been completed.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier:
First received: September 3, 2010
Last updated: November 10, 2015
Last verified: December 2014


- Advanced-stage head and neck cancer (head and neck squamous cell carcinoma [HNSCC]) has moderately successful treatment outcomes, usually involving surgery as part of the standard treatment. Researchers are investigating the use of the drug rapamycin to prevent tumor growth in HNSCC, and are interested in using it to treat individuals with HNSCC that has not been treated previously with other drugs, radiation, or surgery.


- To evaluate the usefulness of rapamycin in decreasing tumor size prior to surgery for head and neck squamous cell carcinoma.


- Individuals at least 18 years of age who have been diagnosed with advanced head and neck squamous cell carcinoma that has not yet been treated.


  • Participants will be screened with a physical examination, medical history, blood tests, and imaging studies.
  • Approximately 1 month before scheduled surgery, participants will begin to receive rapamycin. Participants will take rapamycin once daily for 21 days, followed by a 7-day period without the drug.
  • During the 21-day rapamycin treatment, participants will have weekly study visits to provide blood and urine samples and have possible tumor biopsies and imaging studies such as x-rays or tumor photographs. Participants will have additional study visits for tests 1 day and 1 week after the end of rapamycin treatment, followed by HNSCC surgery.
  • Participants will have a final visit to provide blood samples 30 days after surgery.
  • Participants medical records will be reviewed 1 year after surgery; however, participants will not need to have further study visits at this time.

Condition Intervention Phase
Mouth Neoplasms
Head and Neck Neoplasms
Tongue Neoplasms
Carcinoma, Squamous Cell
Drug: Sirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial Targeting mTOR as a Novel Mechanism-Based Neoadjuvant Therapy for Head and Neck Cancer

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in levels of pS6, pAKt473, and Ki-67 [ Time Frame: 21 days post treatment with rapamycin ] [ Designated as safety issue: No ]
  • Changes in tumor size, blood flow, and standardized uptake value [ Time Frame: 21 days post treatment with rapamycin ] [ Designated as safety issue: No ]
  • Changes in circulating cytokines [ Time Frame: 21 days post treatment with rapamycin ] [ Designated as safety issue: No ]
  • Apoptotic activity and microvessel density [ Time Frame: 21 days post treatment with rapamycin ] [ Designated as safety issue: No ]
  • Clinical and laboratory evaluations for safety [ Time Frame: Pre, during and 30 days post treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety evaluation of rapamycin therapy [ Time Frame: Up to one year post treatment ] [ Designated as safety issue: Yes ]
  • Exploratory studies of possible effects of rapamycin on tumor size [ Time Frame: 21 days post treatment ] [ Designated as safety issue: No ]
  • dynamic CT perfusion, FDG-PET, tumor proliferation, apoptosis, microvessel density and modular changes associated with these effects. [ Time Frame: 21 days post treatment ] [ Designated as safety issue: No ]
  • Survival status, recurrence of disease, metastases, and adverse events/serious adverse events, including complications of wound healing, which are related to rapamycin therapy [ Time Frame: Up to one year post treatment ] [ Designated as safety issue: Yes ]

Enrollment: 3
Study Start Date: August 2010
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Subjects will be treated with sirolimus 21 days
Drug: Sirolimus
21 evaluable subjects will take rapamycin (sirolimus) orally once per day for 21 days. Before and after dosing tumor assessments to include: photographs, CT & amp; PET scans will be done for tumor measurement.

  Show Detailed Description


Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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


Participants must meet all of the following inclusion criteria:

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


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

  1. Surgical resection or chemoradiation of the HNSCC is contraindicated
  2. Prior head or neck squamous cell carcinoma within 5 years, except for previously treated skin cancer
  3. Received chemotherapy targeted monoclonal antibody therapy or investigational therapy within 30 days prior to enrollment
  4. Previous radiation therapy to the head or neck
  5. No measurable tumor remaining after prior biopsy or negative margins from prior biopsy
  6. Inadequate hematologic, renal or liver function within l4 days prior to the first rapamycin dosing visit, as defined by:

    1. Absolute neutrophil count less than 1.5 times 10 (9)/L
    2. 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)
    3. Platelet count less than 100 times 10(9)/L
    4. Hemoglobin less than l0 g/dL (eligibility level for hemoglobin may be reached by transfusion)
    5. AST, ALT or bilirubin greater than 1.5 times the upper limit of local lab normal values
    6. Total cholesterol level greater than 350 mg/dL
    7. Triglyceride level greater than 400 mg/dL
    8. International Normalized Ratio (INR) greater than 1.5
    9. Serum creatinine greater than 1.5mg/dL
  7. Active hepatitis or HBV or HCV infection
  8. 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)
  9. 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)
  10. 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01195922

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Dental and Craniofacial Research (NIDCR)
Principal Investigator: Janice S Lee, DDS, MD National Institute of Dental and Craniofacial Research (NIDCR)
  More Information

Additional Information:
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
Study First Received: September 3, 2010
Last Updated: November 10, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Head and Neck Squamous Cell Carcinoma
Oral Cancer
mTOR Inhibitors
Targeted Therapies
Signal Transduction Inhibitors
Head and Neck Cancer
Squamous Cell Carcinoma
Tongue Cancer

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Mouth Neoplasms
Tongue Neoplasms
Mouth Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Stomatognathic Diseases
Tongue Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 30, 2015