A Phase 1a/1b Study to Evaluate the Safety of EZN-4176, in Adult Patients With Castration-Resistant Prostate Cancer
- Registration Number
- NCT01337518
- Lead Sponsor
- Enzon Pharmaceuticals, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- Male
- Target Recruitment
- 150
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EZN-4176 EZN-4176 -
- Primary Outcome Measures
Name Time Method Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion. 2012 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
Name Time Method Determine the recommended Phase 2 dose of EZN-4176 2013 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).
Trial Locations
- Locations (2)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Institute of Cancer Research, Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom