- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01309490
Phase I/II Study of Ribavirin Given as Monotherapy in Solid Tumour Cancer Patients
An Open-label, Dose Escalation Phase I/II Study of Ribavirin Given as Monotherapy in Solid Tumour Cancer Patients Expressing Elevated eIF4E
Study Overview
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Eftihia Cocolakis, PhD
- Phone Number: 3628 514-340-8222
- Email: ecocolakis@jgh.mcgill.ca
Study Contact Backup
- Name: Nessrine Hanna, MSc
- Phone Number: 6187 514-340-8222
- Email: nhanna@jgh.mcgill.ca
Study Locations
-
-
Quebec
-
Montreal, Quebec, Canada, H3T 1E2
- Recruiting
- Jewish General Hospital
-
Contact:
- Eftihia Cocolakis, PhD
- Phone Number: 3628 514-340-8222
- Email: ecocolakis@jgh.mcgill.ca
-
Principal Investigator:
- Wilson Miller, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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.
- Willing to have a screening biopsy performed from an easily accessible lesion (ex. skin, superficial lymph node) AND whose tumour must overexpress eIF4E.
- 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 (at least 3 weeks).
- Life expectancy ≥ 12 weeks.
- Age ≥ 18 years old.
- 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.
- 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 109/L, platelets ≥ 75 x 109/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 anti-cancer drug within 2 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).
- 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.
Study Plan
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
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Ribavirin-004
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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