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

A Pilot Study to Assess the Pharmacodynamic Effects of Ribavirin in Patients With Tonsil and/or Base of Tongue Squamous Cell Carcinoma

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).

Study Overview

• Status: Completed
• Conditions: HEAD & NECK Cancer
• Intervention / Treatment: Drug: ribavirin

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Explore if Ribavirin Therapy for 2 Weeks Decreases Tumor Expression	of phosphorylated eIF4E among patients with tonsillar squamous cell carcinoma.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to Explore the Pharmacodynamic Effects of Ribavirin	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.	pre-treatment and post treatment
To Explore if Ribavirin Reduces the Expression of HPV-16 Oncoproteins E6 and E7	Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery)	In pre- and post-treatment tumor samples

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: David Pfisher, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Burman B, Drutman SB, Fury MG, Wong RJ, Katabi N, Ho AL, Pfister DG. Pharmacodynamic and therapeutic pilot studies of single-agent ribavirin in patients with human papillomavirus-related malignancies. Oral Oncol. 2022 May;128:105806. doi: 10.1016/j.oraloncology.2022.105806. Epub 2022 Mar 23.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2010
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: December 29, 2010
• First Submitted That Met QC Criteria: December 29, 2010
• First Posted (Estimated): December 31, 2010

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: ribavirin; squamous cell carcinoma; VIRAZOLE; tonsil; base of tongue; 10-218
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: 10-218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No