Ribavirin for Patients With Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies

A Pilot Study of Ribavirin for Patients With Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies

The purpose of this study is to find out the effects, both good and bad, that a drug called ribavirin has on the patient and the cancer.

Ribavirin has also been studied in clinical trials for patients with various types of cancer. These studies demonstrated that ribavirin can be safely given at higher doses than the dosing that is used as part of the treatment of hepatitis C.

Ribavirin is known to target a protein called "4E" that turns on a central part which causes the cell to grow, called the ribosome. HPV-related cancers often have abnormally high levels of 4E. The purpose of this study is to evaluate if ribavirin may be a useful treatment for patients with advanced cancers that are related to HPV by blocking the activity of 4E.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus (HPV)-Related Malignancies; Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
• Intervention / Treatment: Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07939
      • Memorial Sloan Kettering Cancer Center at Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering at Mercy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recurrent and/or metastatic HPV-related carcinoma of the cervix, anus, vagina, vulva, penis, or oropharynx. The cancer diagnosis must be confirmed by slide review in the MSKCC Department of Pathology. HPV positive status must be demonstrated by HPV in situ-hybridization (ISH) and/or by p16 immunohistochemistry (IHC).

Note: For cervix squamous cancer, HPV ISH test or p16 IHC test is not required, because all cervix squamous cancers are presumed to be HPV-associated.

• Adults (≥ 18 years of age)
• ECOG performance status of 1 or better
• Measurable disease according to RECIST 1.1 criteria
• Availability of archived tumor tissue for correlative studies (5 unstained slides)
• Adequate organ function, as follows:
• Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 160 X 109/L, hemoglobin ≥ 10 g/dL
• Hepatic: total bilirubin within ULN (upper limit of normal); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.0 X ULN
• 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.
• Ability to swallow oral medication.
• 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.
• At least one prior systemic therapy regimen for R/M HPV-related carcinoma

Exclusion Criteria:

• History of hemolytic anemia or thalassemia
• Current treatment or known prior treatment with ribavirin
• Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
• Current therapeutic anticoagulation with Coumadin (warfarin)
• Known brain metastases

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; Study subjects will self-administer ribavirin 1400 mg PO BID (total dose, 2800 mg/day). All patients will complete pill diaries to document administration of study drug. Cycle length is 28 days with continuous dosing. Clinic visits for safety assessments and routine laboratory studies will occur weekly in Cycle 1, in weeks 1 and 3 of Cycle 2, and on Week 1 of subsequent cycles. Cross sectional imaging (CT or MRI) is obtained at baseline and q2 cycles and at End-of Treatment (EOT). Response assessments will follow RECIST 1.1 criteria.

Drug: Ribavirin; self-administer ribavirin 1400 mg PO BID (total dose, 2800 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Responses, Determined by RECIST 1.1 Criteria	will be tabulated by adding partial responses and complete responses (CR + PR). The regimen would be considered worthy of further study if radiographic responses are observed in at least 2 of 12 subjects.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Evaluated for Toxicity	will be tabulated using NCI CTCAE version 4,	1 year

Collaborators and Investigators

• Sponsor: 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 2, 2014
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): March 25, 2022

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Actual): January 5, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Ribavirin; Human Papillomavirus (HPV); Recurrent/Metastatic (R/M); 14-211
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: 14-211