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

Not Applicable

Completed

Conditions: Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
Human Papillomavirus (HPV)-Related Malignancies

Interventions: Drug: Ribavirin

Registration Number: NCT02308241

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Radiographic Responses, Determined by RECIST 1.1 Criteria	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Evaluated for Toxicity	1 year	will be tabulated using NCI CTCAE version 4,

Trial Locations

Locations (6): Memorial Sloan Kettering Westchester
🇺🇸
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center at Basking Ridge
🇺🇸
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center @ Suffolk
🇺🇸
Commack, New York, United States
Memorial Sloan Kettering Monmouth
🇺🇸
Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Memorial Sloan Kettering at Mercy Medical Center
🇺🇸
Rockville Centre, New York, United States