Clinical trial NCT02308241: Ribavirin for Patients With Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
Official title: A Pilot Study of Ribavirin for Patients With Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Human Papillomavirus (HPV)-Related Malignancies
Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
Keywords: Ribavirin
Human Papillomavirus (HPV)
Recurrent/Metastatic (R/M)
14-211
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2014-12-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Radiographic Responses, Determined by RECIST 1.1 Criteria
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants Evaluated for Toxicity
timeFrame: 1 year
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering at Mercy Medical Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David Pfister, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.