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

NCT01337518 | Suspended Phase 1

• 1 other identifier: EZN-4176-01
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 2

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.

Conditions

Prostatic Neoplasm

Keywords

Prostate Specific Antigen; Castration Resistant Prostate Cancer; Adenocarcinoma; Androgen Receptor; Metastases

Outcome Measures

Primary Outcomes (1)

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

  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.

  2012

Secondary Outcomes (1)

• Determine the recommended Phase 2 dose of EZN-4176

  2013

Study Arms (1)

EZN-4176

EXPERIMENTAL

Drug: EZN-4176

Interventions

EZN-4176 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)

Also known as: Androgen Receptor mRNA Antagonist

EZN-4176

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Enzon Pharmaceuticals, Inc.: lead

Study Sites (2)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Institute of Cancer Research, Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma; Bulbo-Spinal Atrophy, X-Linked; Neoplasm Metastasis

Interventions

5'-ACCaagtttcttcAGC-3'

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aby Buchbinder, MD

  Enzon Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Daniel Danila, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Johann de Bono, MD

  Institute of Cancer Research, Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2011
• First Posted: April 19, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 18, 2012

Record last verified: 2012-09

Locations

GB (1); US (1)