Pharmacodynamic Effects of Ribavirin in Patients With Tonsil and/or Base of Tongue Squamous Cell Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01268579
First received: December 29, 2010
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

Human papillomavirus (HPV-16) is an important factor in the development of many tonsil and/or base of tongue squamous cell cancers. Although HPV-16 is not thought to cause cancer by itself, it appears to contribute to the development of tonsil and/or base of tongue cancer in many patients. It is likely that treatment for many patients with tonsil and/or base of tongue cancer could be improved if effective therapy to control HPV-16 is developed. The investigators in this study want to learn if ribavirin shows evidence of activity against HPV-16.

Ribavirin is a pill therapy that is approved by the Food and Drug Administration (FDA) as part of the standard treatment for Hepatitis C. Laboratory experiments suggest that ribavirin might also be useful in the treatment of head and neck cancers. However, ribavirin has not yet been tested against head and neck cancer in patients. The purpose of this study is to find out the effects of ribavirin on tonsil and base tongue squamous cell cancer in patients.

The main purpose of this study is to see if ribavirin changes the expression of certain proteins related to HPV infection in the tumor. The study will also find out if ribavirin changes how the tumor appears in a PET/CT scan (positron emission tomography/computed tomography scan).


Condition Intervention
HEAD & NECK Cancer
Drug: ribavirin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study to Assess the Pharmacodynamic Effects of Ribavirin in Patients With Tonsil and/or Base of Tongue Squamous Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To explore if ribavirin therapy for 2 weeks decreases tumor expression [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    of phosphorylated eIF4E among patients with tonsillar squamous cell carcinoma.


Secondary Outcome Measures:
  • to explore the pharmacodynamic effects of ribavirin [ Time Frame: pre-treatment and post treatment ] [ Designated as safety issue: No ]
    on molecules that may be regulated directly or indirectly by eIF4E (eg, p16, p21, EGFR, p53).). Immunohistochemistry will be performed on Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery),to describe the effects of ribavirin treatment on the expression of phosphorylated eIF4E.

  • To explore if ribavirin reduces the expression of HPV-16 oncoproteins E6 and E7 [ Time Frame: In pre- and post-treatment tumor samples ] [ Designated as safety issue: No ]
    Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery)


Estimated Enrollment: 7
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ribavirin
This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.
Drug: ribavirin
The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior diagnostic surgical or core needle biopsy, with confirmation of tonsil and/or base of tongue squamous cell carcinoma that is positive for expression of p16 and phosphorylated eIF4E, as determined by the Department of Pathology at MSKCC. The biopsy may be either of the tonsil base of tongue and/or an involved neck node. 2 unstained slides and/or tissue block must be available from the initial diagnostic biopsy
  • Positive expression p16 and phosphorylated eIF4E is defined as >=30% of tumor cells with cytological and/or nuclear staining
  • Age ≥ 18 and ≤ 65 years of age
  • Karnofsky Performance Status ≥ 80
  • Adequate organ function, as follows:

Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within 1.5 X upper limit of normal (ULN) ; alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 X ULN (Patients with Gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X UNL) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 55 mL/min based on the standard Cockroft and Gault formula.

  • Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
  • Ability to swallow oral medication.
  • Non-surgical patients: If primary radiation +/- chemotherapy (concurrent or sequential) is planned, patients must agree to undergo research biopsy after completion of ribavirin treatment.

Exclusion Criteria:

  • Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
  • More than 10 pack-years of tobacco use
  • History of hemolytic anemia or thalassemia
  • Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
  • Current therapeutic anticoagulation with Coumadin (warfarin)
  • Current or prior treatment with ribavirin
  • Known active Hepatitis B or C
  • Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • Clinically significant peripheral vascular disease
  • History of unstable angina or myocardial infarction (MI) within the last 3 years
  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: NCT01268579

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Matthew Fury, MD,PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01268579     History of Changes
Other Study ID Numbers: 10-218
Study First Received: December 29, 2010
Last Updated: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
ribavirin
VIRAZOLE
tonsil
base of tongue
squamous cell carcinoma
10-218

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Tongue Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Mouth Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Ribavirin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014