A Phase 1a/1b Study to Evaluate the Safety of EZN-4176, in Adult Patients With Castration-Resistant Prostate Cancer
This study has suspended participant recruitment.
(Reassessment of strategic direction)
Information provided by (Responsible Party):
Enzon Pharmaceuticals, Inc.
First received: April 15, 2011
Last updated: December 17, 2012
Last verified: September 2012
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.
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion. [ Time Frame: 2012 ] [ Designated as safety issue: Yes ]
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.
Secondary Outcome Measures:
- Determine the recommended Phase 2 dose of EZN-4176 [ Time Frame: 2013 ] [ Designated as safety issue: Yes ]
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).
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2013 (Final data collection date for primary outcome measure)
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 Name: Androgen Receptor mRNA Antagonist
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01337518
|Memorial Sloan-Kettering Cancer Center
|New York, New York, United States, 10065 |
|Institute of Cancer Research, Royal Marsden Hospital
|Sutton, Surrey, United Kingdom, SM2 5PT |
Enzon Pharmaceuticals, Inc.
||Aby Buchbinder, MD
||Enzon Pharmaceuticals, Inc.
||Daniel Danila, MD
||Memorial Sloan-Kettering Cancer Center
||Johann de Bono, MD
||Institute of Cancer Research, Royal Marsden Hospital
No publications provided
||Enzon Pharmaceuticals, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 15, 2011
||December 17, 2012
||United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Keywords provided by Enzon Pharmaceuticals, Inc.:
Prostate Specific Antigen
Castration Resistant Prostate Cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Site
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs