Phase I/II Study of Ribavirin Given as Monotherapy in Solid Tumour Cancer Patients

March 4, 2011 updated by: Jewish General Hospital

An Open-label, Dose Escalation Phase I/II Study of Ribavirin Given as Monotherapy in Solid Tumour Cancer Patients Expressing Elevated eIF4E

The purpose of this study is to learn whether oral Ribavirin is safe and effective in treating patients with solid tumour cancers, that have high levels of the protein eIF4E.

Study Overview

Status

Unknown

Intervention / Treatment

Detailed Description

This is a dose escalating, open-label, Phase I/II study of single agent oral ribavirin administered daily in solid tumour cancer patients who have failed standard treatments, overexpress eIF4E, and have easily accessible disease for serial biopsies.

Study Type

Interventional

Enrollment (Anticipated)

37

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Jewish General Hospital
        • Contact:
        • Principal Investigator:
          • Wilson Miller, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Phase I part of study : Histologically or cytologically confirmed cancer at diagnosis, with advanced, incurable disease at the time of screening, who have progressed on or are not suitable for standard therapy.

    Phase II part of study: Histologically or cytologically confirmed BC or HNSCC at diagnosis, with advanced, incurable disease at the time of screening, who have progressed on or are not suitable for standard therapy.

  2. Willing to have a screening biopsy performed from an easily accessible lesion (ex. skin, superficial lymph node) AND whose tumour must overexpress eIF4E.
  3. Easily accessible lesion for serial biopsies (ex. skin, superficial lymph node, or other easily accessible site).
  4. At least 1 unidimensionally measurable lesion (based on the RECIST criteria) outside the CNS.
  5. ECOG 0, 1, or 2.
  6. Adequate recovery (excluding alopecia) from previous surgery, radiation, and chemotherapy.
  7. Adequate wash-out period from last therapy (at least 3 weeks).
  8. Life expectancy ≥ 12 weeks.
  9. Age ≥ 18 years old.
  10. Female patients of childbearing potential must have a negative serum (beta-HCG) pregnancy test within 14 days of starting protocol and must not be breastfeeding. Men and women of childbearing potential (including men who have had a vasectomy and women who have had tubal ligation) must agree to use two effective means of contraception throughout the study and for at least 6 months after completion of protocol. Post-menopausal women (defined as 12 or more consecutive months of amenorrhea, or follicle stimulating hormone (FSH) in the post-menopausal range), or surgically sterile women (defined as removal of the uterus or ovaries), do not require methods of contraception.
  11. Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with metastases); serum bilirubin < 1.5 x ULN.
  12. Adequate hematopoietic function: neutrophils ≥ 1.0 x 109/L, platelets ≥ 75 x 109/L.
  13. Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
  14. Accessible for treatment and follow up.

Exclusion Criteria:

  1. Symptomatic brain metastases.
  2. Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.
  3. Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
  4. Use of any investigational anti-cancer drug within 2 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy.
  5. Female patients who are pregnant or breastfeeding.
  6. Concurrent treatment with other anti-cancer therapy. Bisphosphonates are allowed as long as they were started prior to screening (at least 4 weeks before study entry).
  7. Known infection with HIV.
  8. History of other malignancy in the past 5 years. Subjects who have been disease-free for 1 year or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ribavirin, nucleoside analog
Dose Level: 1 1400 mg po BID Dose Level: 2 1800 mg po BID Dose Level: 3 2200 mg po BID Dose Level: 4 2600 mg po BID Dose Level: 5 3000 mg po BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase I: Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D)
Time Frame: Average 1.5 years
Average 1.5 years
Phase II: Determine the overall response rate to therapy with ribavirin
Time Frame: Average 1.5 years
Average 1.5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence and nature of DLTs
Time Frame: 3 years
3 years
Incidence, nature and severity of adverse events
Time Frame: 3 years
3 years
Time to and duration of response, defined as the first occurence of documented objective response until the time of recurrence or death from any cause
Time Frame: 3 years
3 years
Clinical benefit rate, defined as the overall response rate and stable disease for greater than or equal to 24 weeks
Time Frame: 3 years
3 years
Pharmacokinetic parameters of ribavirin determine by total exposure, maximum plasma concentration, etc.
Time Frame: 3 years
3 years
Correlation between eIF4E activity and response
Time Frame: 3 years
3 years
To determine the effect of ribavirin on the activity of eIF4E related pathways through correlative studies
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Anticipated)

March 1, 2014

Study Completion (Anticipated)

June 1, 2014

Study Registration Dates

First Submitted

March 4, 2011

First Submitted That Met QC Criteria

March 4, 2011

First Posted (Estimate)

March 7, 2011

Study Record Updates

Last Update Posted (Estimate)

March 7, 2011

Last Update Submitted That Met QC Criteria

March 4, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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