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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT02308241

Collaborator

(none)

Enrollment

Locations

Arm

87.7

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Human Papillomavirus (HPV)-Related Malignancies Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies	Drug: Ribavirin	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 2, 2014

Actual Primary Completion Date :

Mar 25, 2022

Actual Study Completion Date :

Mar 25, 2022

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

number and grade of toxicities [1 year]
will be tabulated using NCI CTCAE version 4,

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey	United States	07939
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
4	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States