## Protocol Section
### Identification Module
**NCT ID:** NCT01268579

**Brief Title:** Pharmacodynamic Effects of Ribavirin in Patients With Tonsil and/or Base of Tongue Squamous Cell Carcinoma

**Official Title:** A Pilot Study to Assess the Pharmacodynamic Effects of Ribavirin in Patients With Tonsil and/or Base of Tongue Squamous Cell Carcinoma

#### Organization Study ID Info
**ID:** 10-218
#### Organization
**Class:** OTHER
**Full Name:** Memorial Sloan Kettering Cancer Center
### Status Module
#### Completion Date
**Date:** 2022-10-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-10-02

**Type:** ACTUAL

**Last Update Submit Date:** 2023-09-01

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-10-31

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2023-10-02

**Type:** ACTUAL

**Results First Submit Date:** 2023-09-01

**Results First Submit QC Date:** 2023-09-01

#### Start Date
**Date:** 2010-12-28

**Type:** ACTUAL

**Status Verified Date:** 2023-04

#### Study First Post Date
**Date:** 2010-12-31
**Type:** ESTIMATED
**Study First Submit Date:** 2010-12-29
**Study First Submit QC Date:** 2010-12-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Memorial Sloan Kettering Cancer Center

#### Responsible Party

**Type:** SPONSOR

### Description Module

**Brief Summary:** Human papillomavirus (HPV-16) is an important factor in the development of many tonsil and/or base of tongue squamous cell cancers. Although HPV-16 is not thought to cause cancer by itself, it appears to contribute to the development of tonsil and/or base of tongue cancer in many patients. It is likely that treatment for many patients with tonsil and/or base of tongue cancer could be improved if effective therapy to control HPV-16 is developed. The investigators in this study want to learn if ribavirin shows evidence of activity against HPV-16.

Ribavirin is a pill therapy that is approved by the Food and Drug Administration (FDA) as part of the standard treatment for Hepatitis C. Laboratory experiments suggest that ribavirin might also be useful in the treatment of head and neck cancers. However, ribavirin has not yet been tested against head and neck cancer in patients. The purpose of this study is to find out the effects of ribavirin on tonsil and base tongue squamous cell cancer in patients.

The main purpose of this study is to see if ribavirin changes the expression of certain proteins related to HPV infection in the tumor. The study will also find out if ribavirin changes how the tumor appears in a PET/CT scan (positron emission tomography/computed tomography scan).

### Conditions Module

**Conditions:**

- HEAD & NECK Cancer

**Keywords:**

- ribavirin

- VIRAZOLE

- tonsil

- base of tongue

- squamous cell carcinoma

- 10-218

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 9

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

**Intervention Names:**

- Drug: ribavirin

**Label:** ribavirin

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- ribavirin

**Description:** The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.

**Name:** ribavirin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** of phosphorylated eIF4E among patients with tonsillar squamous cell carcinoma.

**Measure:** To Explore if Ribavirin Therapy for 2 Weeks Decreases Tumor Expression

**Time Frame:** 2 weeks

#### Secondary Outcomes

**Description:** on molecules that may be regulated directly or indirectly by eIF4E (eg, p16, p21, EGFR, p53).). Immunohistochemistry will be performed on Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery),to describe the effects of ribavirin treatment on the expression of phosphorylated eIF4E.

**Measure:** to Explore the Pharmacodynamic Effects of Ribavirin

**Time Frame:** pre-treatment and post treatment

**Description:** Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery)

**Measure:** To Explore if Ribavirin Reduces the Expression of HPV-16 Oncoproteins E6 and E7

**Time Frame:** In pre- and post-treatment tumor samples

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Prior diagnostic surgical or core needle biopsy, with confirmation of tonsil and/or base of tongue squamous cell carcinoma that is positive for expression of p16 and phosphorylated eIF4E, as determined by the Department of Pathology at MSKCC. The biopsy may be either of the tonsil base of tongue and/or an involved neck node. 2 unstained slides and/or tissue block must be available from the initial diagnostic biopsy
* Positive expression p16 and phosphorylated eIF4E is defined as \>=30% of tumor cells with cytological and/or nuclear staining
* Age ≥ 18 and ≤ 65 years of age
* Karnofsky Performance Status ≥ 80
* Adequate organ function, as follows:

Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within 1.5 X upper limit of normal (ULN) ; alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 X ULN (Patients with Gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X UNL) 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.

* 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.
* Ability to swallow oral medication.
* Non-surgical patients: If primary radiation +/- chemotherapy (concurrent or sequential) is planned, patients must agree to undergo research biopsy after completion of ribavirin treatment.

Exclusion Criteria:

* Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer
* More than 10 pack-years of tobacco use
* History of hemolytic anemia or thalassemia
* Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment.
* Current therapeutic anticoagulation with Coumadin (warfarin)
* Current or prior treatment with ribavirin
* Known active Hepatitis B or C
* Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* Clinically significant peripheral vascular disease
* History of unstable angina or myocardial infarction (MI) within the last 3 years

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** New York

**Country:** United States

**Facility:** Memorial Sloan Kettering Cancer Center

**State:** New York

**Zip:** 10065

#### Overall Officials

**Official 1:**

**Affiliation:** Memorial Sloan Kettering Cancer Center

**Name:** David Pfisher, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### 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.

**PMID:** 35339025

#### See Also Links

**Label:** Memorial Sloan Kettering Cancer Center

**URL:** http://www.mskcc.org/mskcc/html/44.cfm

## Document Section

### Large Document Module

#### Large Docs

- Date: 2015-04-28

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 864868

- Type Abbrev: Prot_SAP

- Upload Date: 2023-08-31T15:17

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000018307

- Term: Neoplasms, Squamous Cell

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M5550

- Name: Carcinoma, Squamous Cell

- Relevance: HIGH

- As Found: Squamous Cell Carcinoma

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M20451

- Name: Neoplasms, Squamous Cell

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000002294

- Term: Carcinoma, Squamous Cell

### Intervention Browse Module - Ancestors

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M15083

- Name: Ribavirin

- Relevance: HIGH

- As Found: Bevacizumab

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000012254

- Term: Ribavirin

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Ribavirin

**Deaths Num Affected:** 8

**Deaths Num At Risk:** 9

**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.

**ID:** EG000

**Other Num Affected:** 9

**Other Num at Risk:** 9

**Serious Number At Risk:** 9

**Title:** Ribavirin

**Frequency Threshold:** 5

#### Other Events

**Term:** Anemia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Blood and lymphatic system disorders

**Source Vocabulary:** 

**Term:** Dyspnea

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Respiratory, thoracic and mediastinal disorders

**Source Vocabulary:** 

**Term:** Blood bilirubin increase

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** 

**Term:** Fatigue

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** Anorexia

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Metabolism and nutrition disorders

**Source Vocabulary:** 

**Term:** Aspartate aminotransferase increase

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** 

**Term:** Fever

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** General disorders

**Source Vocabulary:** 

**Term:** Gastroesophageal Reflux

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Gastrointestinal disorders

**Source Vocabulary:** 

**Term:** Weight loss

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** 

**Term:** Alanine aminotransferase increase

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** 

**Term:** Alkaline phosphatase increase

**Assessment Type:** SYSTEMATIC_ASSESSMENT

**Organ System:** Investigations

**Source Vocabulary:** 

**Time Frame:** Up to 1 year

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 9

**Units:** Participants

### Group

**ID:** BG000

**Title:** Ribavirin

**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.

### Measure

#### Measurement

**Group ID:** BG000

**Lower Limit:** 47

**Upper Limit:** 69

**Value:** 59

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 2

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 7

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 1

**Category Title:** Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 5

**Category Title:** Not Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 3

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 7

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 2

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 9

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** FULL_RANGE
**Parameter Type:** MEDIAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Ethnicity (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Region of Enrollment
**Unit of Measure:** Participants
## Results Section - More Information Module
### Certain Agreement
**PI Sponsor Employee:** True
### Point of Contact
**Email:** pfisterd@MSKCC.ORG
**Organization:** Memorial Sloan Kettering Cancer Center
**Phone:** 646-888-4237
**Title:** Dr. David Pfister MD
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 4
**Title:** Decreased p-eIF4E after 14 days of ribavirin
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 2
**Title:** No decreased p-eIF4E after 14 days of ribavirin
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 
- **Upper Limit:** 
- **Value:** 3
**Title:** Not evaluable
#### Outcome Measure 2
#### Outcome Measure 3
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** of phosphorylated eIF4E among patients with tonsillar squamous cell carcinoma.
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** To Explore if Ribavirin Therapy for 2 Weeks Decreases Tumor Expression
**Type:** PRIMARY
**Unit of Measure:** Participants
##### Group
**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.
**ID:** OG000
**Title:** Ribavirin
#### Outcome Measure 2
**Description:** on molecules that may be regulated directly or indirectly by eIF4E (eg, p16, p21, EGFR, p53).). Immunohistochemistry will be performed on Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery),to describe the effects of ribavirin treatment on the expression of phosphorylated eIF4E.
**Population Description:** N/A - data were not collected
**Reporting Status:** POSTED
**Time Frame:** pre-treatment and post treatment
**Title:** to Explore the Pharmacodynamic Effects of Ribavirin
**Type:** SECONDARY
##### Group
**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.
**ID:** OG000
**Title:** Ribavirin
#### Outcome Measure 3
**Description:** Pathology samples (e.g. diagnostic biopsy), as well as on the post-treatment surgical pathology samples (e.g. definitive surgery)
**Population Description:** N/A - data were not collected
**Reporting Status:** POSTED
**Time Frame:** In pre- and post-treatment tumor samples
**Title:** To Explore if Ribavirin Reduces the Expression of HPV-16 Oncoproteins E6 and E7
**Type:** SECONDARY
##### Group
**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.
**ID:** OG000
**Title:** Ribavirin
### Participant Flow Module
#### Group
**Description:** This will be a single institution non-randomized study for patients with tonsil and/or base of tongue squamous cell cancer. This is a pilot study to obtain pharmacodynamic data regarding the effects of ribavirin on tonsil squamous cell cancer.

ribavirin: The clinical intervention in this study is ribavirin therapy for approximately 14 days. Ribavirin 800 mg/day is administered in divided doses, 400 mg PO qAM and 400 mg PO qPM.
**ID:** FG000
**Title:** Ribavirin
#### Period
**Title:** Overall Study
##### Withdraw
**Type:** Adverse Event
###### Reason
**Group ID:** FG000
**Number of Subjects:** 1
##### Withdraw
**Type:** Withdrawal by Subject
###### Reason
**Group ID:** FG000
**Number of Subjects:** 2
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 9
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 3
**Has Results:** True