A Phase 1a/1b Study to Evaluate the Safety of EZN-4176, in Adult Patients With Castration-Resistant Prostate Cancer

NCT ID: NCT01337518

Last Updated: 2012-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2013-12-31

Brief Summary

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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

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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.

Conditions

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Prostatic Neoplasm

Keywords

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Prostate Specific Antigen Castration Resistant Prostate Cancer Adenocarcinoma Androgen Receptor Metastases

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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EZN-4176

Group Type EXPERIMENTAL

EZN-4176

Intervention Type DRUG

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)

Interventions

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EZN-4176

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)

Intervention Type DRUG

Other Intervention Names

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Androgen Receptor mRNA Antagonist

Eligibility Criteria

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Inclusion Criteria

1. Capable of understanding protocol requirements \& risks \& providing written informed consent
2. Histologically or cytologically confirmed diagnosis of metastatic prostate adenocarcinoma
3. Ongoing gonadal androgen-deprivation therapy with LHRH analogs or orchiectomy. Patients without orchiectomy must receive effective LHRH analog therapy during the study
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 EZN-4176
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
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Enzon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aby Buchbinder, MD

Role: STUDY_DIRECTOR

Enzon Pharmaceuticals, Inc.

Daniel Danila, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Johann de Bono, MD

Role: PRINCIPAL_INVESTIGATOR

Institute of Cancer Research, Royal Marsden Hospital

Locations

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Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Institute of Cancer Research, Royal Marsden Hospital

Sutton, Surrey, United Kingdom

Site Status

Countries

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United States United Kingdom

Other Identifiers

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EZN-4176-01

Identifier Type: -

Identifier Source: org_study_id