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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

Phase 1
18 Years
Not Enrolling
Prostatic Neoplasm

Thank you

Trial Information

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 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.

Inclusion Criteria:

1. Capable of understanding protocol requirements & risks & providing written informed

2. Histologically or cytologically confirmed diagnosis of metastatic prostate

3. Ongoing gonadal androgen-deprivation therapy with LHRH analogs or orchiectomy.
Patients without orchiectomy must receive effective LHRH analog therapy during the

4. Testosterone < 50 ng/dL

5. 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

6. 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.

7. Patients who failed standard therapy or who, after physician discussion, wish to
delay chemotherapy

8. Age ≥ 18 yrs

9. ECOG Score: 0-1

10. Albumin ≥3.0 g/dL

11. ANC ≥ 1,500/µL

12. Plts ≥ 75,000/µL

13. Hgb ≥ 9.0 g/dL

14. Serum Creat. ≤ 1.5xULN or Calc Creat. clearance ≥ 60 mL/min

15. Tot bili ≤ 1.5xULN

16. AST; ALT: ≤ 2.5xULN

Exclusion Criteria:

1. Prostate cancer other than adenocarcinoma, eg. neuroendocrine or small cell histology

2. Concurrent serious medical illness that might interfere with protocol compliance

3. Known chronic infectious disease, eg. AIDS or hepatitis

4. 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.

5. History of CNS tumor involvement

6. 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)

7. > 10 mg/day of prednisone or equivalent systemic corticosteroid within 4 weeks of
first dose of EZN-4176

8. 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.

9. 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

10. 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

11. 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

12. 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

13. 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

14. Inability to comply with study protocol

15. Full anticoagulation therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion.

Outcome Description:

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.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Aby Buchbinder, MD

Investigator Role:

Study Director

Investigator Affiliation:

Enzon Pharmaceuticals, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

March 2011

Completion Date:

December 2013

Related Keywords:

  • Prostatic Neoplasm
  • Prostate Specific Antigen
  • Castration Resistant Prostate Cancer
  • Adenocarcinoma
  • Androgen Receptor
  • Metastases
  • Neoplasms
  • Prostatic Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021