Human Papillomavirus (HPV)-Related Malignancies, Recurrent/Metastatic (R/M) Human Papillomavirus (HPV)-Related Malignancies
Conditions
Keywords
Ribavirin, Human Papillomavirus (HPV), Recurrent/Metastatic (R/M), 14-211
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.
Interventions
DRUGRibavirin
self-administer ribavirin 1400 mg PO BID (total dose, 2800 mg/day)
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Evaluated for Toxicity | 1 year | will be tabulated using NCI CTCAE version 4, |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Ribavirin: self-administer ribavirin 1400 mg PO BID (total dose, 2800 mg/day) | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Ribavirin |
|---|---|
| Age, Continuous | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
Primary
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.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ribavirin | Radiographic Responses, Determined by RECIST 1.1 Criteria | Stable Disease | 5 Participants |
| Ribavirin | Radiographic Responses, Determined by RECIST 1.1 Criteria | Progression of Disease | 4 Participants |
| Ribavirin | Radiographic Responses, Determined by RECIST 1.1 Criteria | Unevaluable | 3 Participants |
Secondary
Number of Participants Evaluated for Toxicity
will be tabulated using NCI CTCAE version 4,
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ribavirin | Number of Participants Evaluated for Toxicity | 12 Participants |