Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Dental and Craniofacial Research (NIDCR) )
ClinicalTrials.gov Identifier:
NCT01195922
First received: September 3, 2010
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

Background:

- 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.

Objectives:

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

Eligibility:

- 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.

Design:

  • 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: Rapamycin
Procedure: Biopsy
Procedure: Dynamic CT Perfusion
Procedure: Positron Emission Tomography
Procedure: Measurement Serum Cytokines
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:
  • Evaluate the antitumoral activity of rapamycin in HNSCC patients in terms of objective responses; investigate underlying molecular changes to identify biomarkers for understanding, monitoring, and predicting a clinical response to rapamycin in H...

Secondary Outcome Measures:
  • Safety evaluation of rapamycin therapy prior to surgery; dynamic CT perfusion, and FDG-PET; evaluation of tumor proliferation, apoptosis, microvessel density and the underlying molecular changes

Estimated Enrollment: 50
Study Start Date: August 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Rapamycin
    N/A
    Procedure: Biopsy
    N/A
    Procedure: Dynamic CT Perfusion
    N/A
    Procedure: Positron Emission Tomography
    N/A
    Procedure: Measurement Serum Cytokines
    N/A
  Show Detailed Description

  Eligibility

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

  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

EXCLUSION CRITERIA:

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

Contacts
Contact: Patrice R Williams Yohannes, R.N. (301) 402-6905 williamspr@mail.nih.gov
Contact: J. Silvio Gutkind, Ph.D. (301) 496-2069 gutkind@dir.nidcr.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Investigators
Principal Investigator: J. Silvio Gutkind, Ph.D. National Institute of Dental and Craniofacial Research (NIDCR)
  More Information

Additional Information:
Publications:
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: March 14, 2014
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:
Tongue Diseases
Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Mouth Neoplasms
Tongue Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 24, 2014