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A Phase I/II Exploratory Study of Ribavirin in Metastatic Breast Cancer Expressing Elevated eIF4E

Phase 1/Phase 2
18 Years
Not Enrolling
Metastatic Breast Cancer

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Trial Information

A Phase I/II Exploratory Study of Ribavirin in Metastatic Breast Cancer Expressing Elevated eIF4E

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.

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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate to therapy with daily oral ribavirin

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Wilson Miller, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jewish General Hospital


Canada: Health Canada

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Metastatic Breast Cancer
  • metastatic breast cancer
  • ribavirin
  • eIF4E
  • Breast Neoplasms