- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01337518
A Phase 1a/1b Study to Evaluate the Safety of EZN-4176, in Adult Patients With Castration-Resistant Prostate Cancer
December 17, 2012 updated by: Enzon Pharmaceuticals, Inc.
A Phase 1a/1b, Open-Label Study Evaluating the Safety and Tolerability of EZN-4176, an Androgen Receptor mRNA Antagonist, in Adult Patients With Castration-Resistant Prostate Cancer
This study will evaluate an experimental drug called EZN-4176 to determine the anticancer effects when it is given to patients with an advanced form of prostate cancer called castration-resistant prostate cancer (CRPC).
Goals of this phase I study include finding out the dose of EZN-4176 that can be safely given without serious side effects and to determine the amount of EZN-4176 that should be given in future studies.
Study Overview
Detailed Description
This study will be conducted in two phases:
- Phase 1a will involve dose escalation to determine the maximum tolerated dose (MTD). The MTD will be determined on the basis of the results from the safety evaluation.
- Phase 1b will involve cohort expansion at one or more dose levels to determine the recommended Phase 2 dose. The recommended Phase 2 dose, which may differ from the MTD, will be determined on the basis of results from safety, activity, and pharmacologic and correlative studies.
Study Type
Interventional
Enrollment (Anticipated)
150
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Surrey
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Sutton, Surrey, United Kingdom, SM2 5PT
- Institute of Cancer Research, Royal Marsden Hospital
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Capable of understanding protocol requirements & risks & providing written informed consent
- Histologically or cytologically confirmed diagnosis of metastatic prostate adenocarcinoma
- Ongoing gonadal androgen-deprivation therapy with LHRH analogs or orchiectomy. Patients without orchiectomy must receive effective LHRH analog therapy during the study
- Testosterone < 50 ng/dL
- Progressive disease after androgen deprivation - with all 3 of the following criteria:PSA evidence of progressive prostate cancer; PSA ≥ 5 ng/mL increasing on at least 2 successive occasions, at least 2 weeks apart. If confirmatory PSA < screening PSA, additional test for increasing PSA is needed
- Patients receiving anti-androgen agent as part of primary androgen ablation: disease progression after stopping the anti-androgen agent. This disease progression is defined: 2 consecutive increasing PSAs ≥ 2 weeks apart, or documented osseous or soft tissue progression. Flutamide patients: at least one of the PSAs ≥ 4 weeks after stopping flutamide. Bicalutamide or nilutamide patients: at least one PSA ≥ 6 weeks after stopping the anti-androgen agent.
- Patients who failed standard therapy or who, after physician discussion, wish to delay chemotherapy
- Age ≥ 18 yrs
- ECOG Score: 0-1
- Albumin ≥3.0 g/dL
- ANC ≥ 1,500/µL
- Plts ≥ 75,000/µL
- Hgb ≥ 9.0 g/dL
- Serum Creat. ≤ 1.5xULN or Calc Creat. clearance ≥ 60 mL/min
- Tot bili ≤ 1.5xULN
- AST; ALT: ≤ 2.5xULN
Exclusion Criteria:
- Prostate cancer other than adenocarcinoma, eg. neuroendocrine or small cell histology
- Concurrent serious medical illness that might interfere with protocol compliance
- Known chronic infectious disease, eg. AIDS or hepatitis
- Male patient of reproductive capacity unwilling to use methods appropriate to prevent pregnancy. In the UK, double-barrier contraception required. Patients should continue to use contraception for 3 months after stopping EZN-4176 due to potential for prolonged half-life of EZN-4176 in the liver.
- History of CNS tumor involvement
- Other hormonal therapy, eg. megestrol acetate (Megace®), finasteride (Proscar®), dutasteride (Avodart®), or any herbal product known to decrease PSA (e.g., saw palmetto, PC-SPES, and PC-HOPE)
- > 10 mg/day of prednisone or equivalent systemic corticosteroid within 4 weeks of first dose of EZN-4176
- Initiation of bisphosphonates within 4 weeks of enrollment. Patients receiving stable doses of bisphosphonates with subsequent tumor progression may continue to receive this medication; however, initiation of bisphosphonates is not allowed during the study.
- Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following: Conventional multivitamin supplements; Selenium; Lycopene; and Soy supplements
- Prior chemotherapy, immunotherapy, investigational therapeutic agent, or other therapy used to treat the cancer within 4 weeks (6 weeks for prior treatment with mitomycin C or nitrosoureas) before first dose of EZN-4176
- Radiation or radioactive treatment within 4 weeks before first dose of EZN-4176. Single-fraction palliative radiation is allowed within 2 weeks before first dose of EZN-4176
- Lack of recovery from any reversible side effects (except alopecia and Grade 1 or 2 neuropathy) to Grade 0 or 1 toxicity related to administration of an investigational therapeutic agent, chemotherapy, immunotherapy, radiotherapy, or other agents previously used to treat the cancer
- Current participation in another clinical study with an investigational therapeutic agent and/or use of an investigational therapeutic drug (not including investigational use of an approved drug) in the 30 days before first dose of EZN-4176
- Inability to comply with study protocol
- Full anticoagulation therapy
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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 |
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Experimental: EZN-4176
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EZN-4176 can be administered as a weekly one-hour i.v.
infusion; weekly for 3 weeks followed by a 1 week rest; or 1 out of 2 weeks (every other week)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion.
Time Frame: 2012
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Evaluate incidence, severity and duration of adverse events using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0, during first cycle.
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2012
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine the recommended Phase 2 dose of EZN-4176
Time Frame: 2013
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Incidence, severity and duration of adverse events using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0, during all cycles; Objective response, as assessed per recommendations of the Prostate Cancer Clinical Trials Working Group (PCWG2).
|
2013
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Johann de Bono, MD, Institute of Cancer Research, Royal Marsden Hospital
- Study Director: Aby Buchbinder, MD, Enzon Pharmaceuticals, Inc.
- Principal Investigator: Daniel Danila, MD, Memorial Sloan Kettering Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2011
Primary Completion (Anticipated)
December 1, 2013
Study Completion (Anticipated)
December 1, 2013
Study Registration Dates
First Submitted
April 15, 2011
First Submitted That Met QC Criteria
April 18, 2011
First Posted (Estimate)
April 19, 2011
Study Record Updates
Last Update Posted (Estimate)
December 18, 2012
Last Update Submitted That Met QC Criteria
December 17, 2012
Last Verified
September 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EZN-4176-01
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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