Treatment With Ribavirin for Patients With Metastatic Breast Cancer

This study has been terminated.
(Study closed because of new overlapping study with ribavirin.)
Sponsor:
Information provided by (Responsible Party):
Wilson Miller, Jewish General Hospital
ClinicalTrials.gov Identifier:
NCT01056757
First received: January 25, 2010
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to learn whether oral Ribavirin is safe and effective in treating patients with metastatic breast cancer, that have high levels of eIF4E.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Ribavirin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Exploratory Study of Ribavirin in Metastatic Breast Cancer Expressing Elevated eIF4E

Resource links provided by NLM:


Further study details as provided by Jewish General Hospital:

Primary Outcome Measures:
  • Overall response rate to therapy with daily oral ribavirin [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to and duration of response [ Time Frame: 1-5years ] [ Designated as safety issue: No ]
  • Time to relapse [ Time Frame: 1-5 years ] [ Designated as safety issue: No ]
  • To determine the medical risk (safety and tolerability) that ribavirin may have on breast cancer patients as determined by laboratory tests, vital signs, and clinical adverse events. [ Time Frame: 1-2 years ] [ Designated as safety issue: Yes ]
  • Correlation between activity of eIF4E and response [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]
  • Effect of ribavirin on the activity of eIF4E related pathways [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]
  • Evaluate pharmacokinetic parameters of ribavirin [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]
  • Correlate expression of eIF4E in fresh and archived tissue [ Time Frame: 1-2 years ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: December 2009
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ribavirin Drug: Ribavirin
1000 mg bid, po, q28days

Detailed Description:

Overexpression of eIF4E occurs in greater than 50% of BC, where it has been associated with clinical progression, angiogenesis and chemoresistance. eIF4E protein expression is not elevated in stroma or in benign tissue. A major focus in the future management of BC is to develop novel targeted therapeutics, with associated biomarkers of clinical value. It is possible that targeting a central regulator that can control multiple pathways might be more effective than targeting a single downstream molecule. In our preclinical studies, we have demonstrated that ribavirin inhibits proliferation of BC cell lines at clinically achievable concentrations by inhibiting its target, eIF4E. This trial addresses the important clinical issue of the lack of treatment for poor prognosis BC, characterized by overexpression of eIF4E. We will explore the use of eIF4E as therapeutic target and a predictive marker. We will determine whether targeting eIF4E with ribavirin, a commercially approved, inexpensive, oral therapeutic compound with a favourable toxicity profile, may present a novel treatment option for patients with aggressive, metastatic disease.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed breast cancer at diagnosis, with metastatic disease at the time of screening, who have progressed on prior anthracycline and taxane-containing regimens.
  • Willing to have a screening biopsy performed from an easily accessible lesion (ex. skin, superficial lymph node), AND must have overexpression of eIF4E in the metastatic tissue.
  • Easily accessible lesion for serial biopsies (ex. skin, superficial lymph node, or other easily accessible site).
  • At least 1 unidimensionally measurable lesion (based on the RECIST criteria) outside the CNS.
  • ECOG 0, 1, or 2.
  • Adequate recovery (excluding alopecia) from previous surgery, radiation, and chemotherapy.
  • Adequate wash-out period from last therapy for breast cancer (at least 3 weeks).
  • Life expectancy ≥ 12 weeks.
  • Age is ≥ 18 years. There is no upper age limit since the drug can be administered orally and even considered in a palliative setting.
  • 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 must agree to use an 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, do not require methods of contraception.
  • 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.
  • Adequate hematopoietic function: neutrophils ≥1.0 x 10E9/L, platelets ≥ 100 x 10E9/L.
  • Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.
  • Accessible for treatment and follow up.

Exclusion Criteria:

  • Symptomatic brain metastases.
  • Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.
  • Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
  • Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy.
  • Female patients who are pregnant or breastfeeding.
  • 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) and the dose does not change during study participation.
  • Known infection with HIV.
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01056757

Locations
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Jewish General Hospital
Investigators
Principal Investigator: Wilson Miller, MD, PhD Jewish General Hospital
Study Director: Katherine Borden, PhD Université de Montréal
  More Information

Publications:
Responsible Party: Wilson Miller, Principal Investigator, Jewish General Hospital
ClinicalTrials.gov Identifier: NCT01056757     History of Changes
Other Study ID Numbers: Ribavirin-003
Study First Received: January 25, 2010
Last Updated: June 21, 2013
Health Authority: Canada: Health Canada

Keywords provided by Jewish General Hospital:
metastatic breast cancer
ribavirin
eIF4E

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

ClinicalTrials.gov processed this record on April 21, 2014