Rapamycin Therapy in Head and Neck Squamous Cell Carcinoma

NCT01195922 | Completed Phase 1 Results DMC

• 2 other identifiers: 10018010-D-0180
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mouth Neoplasms; Head and Neck Neoplasms; Tongue Neoplasms; Carcinoma, Squamous Cell

Keywords

Head and Neck Squamous Cell Carcinoma; Oral Cancer; mTOR Inhibitors; Targeted Therapies; Signal Transduction Inhibitors; Head and Neck Cancer; Squamous Cell Carcinoma; Tongue Cancer

Outcome Measures

Primary Outcomes (3)

• Percent (%) Change in Levels of pS6, pAKt473, and Ki-67

  21 days post treatment with rapamycin

• Percent (%) Changes in Tumor Size, Blood Flow, and Standardized Uptake Value

  21 days post treatment with rapamycin

• Percent (%) Change in Clinical and Laboratory Evaluations for Safety

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

Study Arms (1)

Sirolimus

EXPERIMENTAL

Subjects will be treated with sirolimus 21 days

Drug: Sirolimus

Interventions

Sirolimus DRUG

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.

Also known as: Rapamycin

Sirolimus

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

  PMID: 18287387 BACKGROUND

• Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med. 2001 Dec 27;345(26):1890-900. doi: 10.1056/NEJMra001375. No abstract available.

  PMID: 11756581 BACKGROUND

• Agulnik M, da Cunha Santos G, Hedley D, Nicklee T, Dos Reis PP, Ho J, Pond GR, Chen H, Chen S, Shyr Y, Winquist E, Soulieres D, Chen EX, Squire JA, Marrano P, Kamel-Reid S, Dancey J, Siu LL, Tsao MS. Predictive and pharmacodynamic biomarker studies in tumor and skin tissue samples of patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with erlotinib. J Clin Oncol. 2007 Jun 1;25(16):2184-90. doi: 10.1200/JCO.2006.07.6554.

  PMID: 17538163 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Mouth Neoplasms; Head and Neck Neoplasms; Tongue Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Tongue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: D. J. Silvio Gutkind
• Organization: University of California San Diego

sgutkind@ucsd.edu

(858) 534 5980

Study Officials

• Janice S Lee, DDS, MD

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 6, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 6, 2017
• Results First Posted: January 19, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)