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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Jewish General Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Jewish General Hospital
ClinicalTrials.gov Identifier:
NCT01309490
First received: March 4, 2011
Last updated: NA
Last verified: March 2011
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Malignant Solid Tumour
Drug: Ribavirin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Dose Escalation Phase I/II Study of Ribavirin Given as Monotherapy in Solid Tumour Cancer Patients Expressing Elevated eIF4E

Resource links provided by NLM:


Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:
  • Phase I: Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) [ Time Frame: Average 1.5 years ] [ Designated as safety issue: Yes ]
  • Phase II: Determine the overall response rate to therapy with ribavirin [ Time Frame: Average 1.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and nature of DLTs [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Incidence, nature and severity of adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Clinical benefit rate, defined as the overall response rate and stable disease for greater than or equal to 24 weeks [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of ribavirin determine by total exposure, maximum plasma concentration, etc. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Correlation between eIF4E activity and response [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • To determine the effect of ribavirin on the activity of eIF4E related pathways through correlative studies [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 37
Study Start Date: March 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ribavirin, nucleoside analog Drug: Ribavirin
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309490

Contacts
Contact: Eftihia Cocolakis, PhD 514-340-8222 ext 3628 ecocolakis@jgh.mcgill.ca
Contact: Nessrine Hanna, MSc 514-340-8222 ext 6187 nhanna@jgh.mcgill.ca

Locations
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Contact: Eftihia Cocolakis, PhD    514-340-8222 ext 3628    ecocolakis@jgh.mcgill.ca   
Principal Investigator: Wilson Miller, MD, PhD         
Sponsors and Collaborators
Jewish General Hospital
  More Information

Publications:
Responsible Party: Wilson Miller, Jewish General Hospital - McGill University
ClinicalTrials.gov Identifier: NCT01309490     History of Changes
Other Study ID Numbers: Ribavirin-004
Study First Received: March 4, 2011
Last Updated: March 4, 2011
Health Authority: Canada: Health Canada

Keywords provided by Jewish General Hospital:
high eIF4E expression
solid tumor cancer

Additional relevant MeSH terms:
Neoplasms
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014