Treatment With Ribavirin for Patients With Metastatic Breast Cancer

NCT01056757 | Terminated Phase 1

• 1 other identifier: Ribavirin-003
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Keywords

metastatic breast cancer; ribavirin; eIF4E

Outcome Measures

Primary Outcomes (1)

• Overall response rate to therapy with daily oral ribavirin

  2 years

Secondary Outcomes (7)

• Time to and duration of response

  1-5years

• Time to relapse

  1-5 years

• 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.

  1-2 years

• Correlation between activity of eIF4E and response

  1-2 years

• Effect of ribavirin on the activity of eIF4E related pathways

  1-2 years

Study Arms (1)

Ribavirin

EXPERIMENTAL

Drug: Ribavirin

Interventions

Ribavirin DRUG

1000 mg bid, po, q28days

Ribavirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jewish General Hospital: lead

Study Sites (1)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (4)

• Kentsis A, Topisirovic I, Culjkovic B, Shao L, Borden KL. Ribavirin suppresses eIF4E-mediated oncogenic transformation by physical mimicry of the 7-methyl guanosine mRNA cap. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18105-10. doi: 10.1073/pnas.0406927102. Epub 2004 Dec 15.

  PMID: 15601771 BACKGROUND

• Assouline S, Culjkovic B, Cocolakis E, Rousseau C, Beslu N, Amri A, Caplan S, Leber B, Roy DC, Miller WH Jr, Borden KL. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin. Blood. 2009 Jul 9;114(2):257-60. doi: 10.1182/blood-2009-02-205153. Epub 2009 May 11.

  PMID: 19433856 BACKGROUND

• Coleman LJ, Peter MB, Teall TJ, Brannan RA, Hanby AM, Honarpisheh H, Shaaban AM, Smith L, Speirs V, Verghese ET, McElwaine JN, Hughes TA. Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer. 2009 May 5;100(9):1393-9. doi: 10.1038/sj.bjc.6605044. Epub 2009 Apr 14.

  PMID: 19367274 BACKGROUND

• Holm N, Byrnes K, Johnson L, Abreo F, Sehon K, Alley J, Meschonat C, Md QC, Li BD. A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-negative breast cancer. Ann Surg Oncol. 2008 Nov;15(11):3207-15. doi: 10.1245/s10434-008-0086-9. Epub 2008 Aug 22.

  PMID: 18719964 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Wilson Miller, MD, PhD

  Jewish General Hospital

  PRINCIPAL INVESTIGATOR

• Katherine Borden, PhD

  Université de Montréal

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2010
• First Posted: January 26, 2010
• Study Start: December 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: November 4, 2015

Record last verified: 2015-11

Locations

CA (1)