Prostatic NeoplasmPhase 1NCT01337518
A Phase 1a/1b Study to Evaluate the Safety of EZN-4176, in Adult Patients With Castration-Resistant Prostate Cancer
A Phase 1 study testing EZN-4176 in people with Prostatic Neoplasm, run by Enzon Pharmaceuticals, Inc. at 2 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasm
- What is being tested?
- EZN-4176
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2011to Dec 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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)
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- > 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
United Kingdom1 site
Institute of Cancer Research, Royal Marsden Hospital
Sutton, Surrey, SM2 5PT
About this study
Official title: 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 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.
Read the 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.
- Conditions
- Prostatic Neoplasm
- Being tested
- EZN-4176
- Keywords
- Prostate Specific Antigen, Castration Resistant Prostate Cancer, Adenocarcinoma, Androgen Receptor, Metastases
- Medical subject headings
- Prostatic Neoplasms, Adenocarcinoma, Bulbo-Spinal Atrophy, X-Linked, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EZN-4176Drug
Also called Androgen Receptor mRNA Antagonist
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)
| Study group | Role | What they receive |
|---|---|---|
| EZN-4176 | Experimental | Not described Receives: Drug: EZN-4176 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2012
Secondary outcomes (1)
Determine the recommended Phase 2 dose of EZN-4176
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).
Measured: 2013
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Why it stopped: Reassessment of strategic direction
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Enzon Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aby Buchbinder, MD, Study director, Enzon Pharmaceuticals, Inc.Daniel Danila, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterJohann de Bono, MD, Principal investigator, Institute of Cancer Research, Royal Marsden Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01337518
- Sponsor's protocol ID
- EZN-4176-01
- Status last verified
- Sep 2012
- First submitted
- 15 Apr 2011
- Last updated
- 18 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01337518
- Acronym / sponsor ID
- EZN-4176-01
- Conditions
- Prostatic Neoplasm
- Keywords
- Prostate Specific Antigen, Castration Resistant Prostate Cancer, Adenocarcinoma, Androgen Receptor, Metastases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Reassessment of strategic direction
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Enzon Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 19 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EZN-4176 | Experimental | Drug: EZN-4176 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EZN-4176Also: Androgen Receptor mRNA AntagonistEZN-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) | Drug | EZN-4176 |
Primary outcome
Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion.
Time frame: 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.
1 secondary outcome
Determine the recommended Phase 2 dose of EZN-4176
Time frame: 2013
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aby Buchbinder, MD study director
Enzon Pharmaceuticals, Inc.
Daniel Danila, MD principal investigator
Memorial Sloan Kettering Cancer Center
Johann de Bono, MD principal investigator
Institute of Cancer Research, Royal Marsden Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EZN-4176 in people with Prostatic Neoplasm, run by Enzon Pharmaceuticals, Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 18 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the Maximum Tolerated Dose (MTD) of EZN-4176 administered as a weekly 1-hour IV infusion. (time frame: 2012). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2012.