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Adenocarcinoma of the ProstatePhase 2NCT02058706

LHRH Analogue Therapy With Enzalutamide or Bicalutamide in Treating Patients With Hormone Sensitive Prostate Cancer

A Phase 2 study testing enzalutamide, bicalutamide and orchiectomy in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by Barbara Ann Karmanos Cancer Institute at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized phase II trial studies if enzalutamide added to standard luteinizing hormone-releasing hormone (LHRH) analogue therapy will improve effects against prostate cancer compared to the standard therapy of LHRH analogue and bicalutamide. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
enzalutamide, bicalutamide and orchiectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
4 sitesUnited States
Study dates
May 2014to 1 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy. [Late induction permitted within 3 months of starting LHRH analogue therapy or antiandrogen]
  • All patients who have not initiated hormone therapy (Early induction patients) must have elevated PSA ≥ 4 ng/ml within 28 days prior to registration. For late induction registrations, PSA must be ≥ 4 ng/ml prior to start of androgen deprivation therapy; either antiandrogen or LHRH analogue or GNRH antagonist .If patients are on antiandrogen, this will need to be discontinued for at least 7 days prior to registration.
  • Patients with a history of prior neoadjuvant or adjuvant hormone therapy are eligible provided they have received twenty four or less months of hormone treatment (single or combination treatment, excluding orchiectomy). Both therapies (neoadjuvant/adjuvant hormone therapy) must have been discontinued at least 6 months prior to registration. This is intended to exclude patients who might have been rendered indirectly androgen insensitive.
  • There must be no plans to receive concomitant chemotherapy, biological response modifiers, radiation therapy or hormonal therapy. Concomitant radiation therapy is allowed for the palliation of severe pain/neuropathic compression. Prior or concomitant use of megestrol acetate for the treatment of hot flashes is allowed.
  • Patients must have a performance status of 0 - 2 by Zubrod Criteria.
  • Patients must have recovered from any major infections and/or surgical procedures and,in the opinion of the investigator, not have significant active medical illness precluding protocol treatment or survival.
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  • No prior malignancy is allowed except for adequately treated basal cell (or squamous cell) skin cancer, superficial or in situ cancer of the bladder. For an invasive cancer the patients should be disease free for at least 3 years prior to enrollment on study.
  • For all patients a bone scan must be performed within 60 days prior to registration for tumor assessment. CT scans (abdomen and pelvis) and chest x-ray are optional, but must be repeated if used for disease assessment. For late induction registrations, tumor assessment imaging showing metastatic disease must be available prior to start of androgen deprivation therapy.
  • Age 18 or older and willing and able to provide informed consent.
  • Willingness to swallow pills and no medical condition that would interfere with this.
  • Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Patients are also required to use a condom if having sex with a pregnant woman.
  • Patient should agree to a tumor tissue biopsy prior to protocol enrollment. Post therapy biopsy is optional.
  • Patients who are being treated with a GNRH antagonist should be willing to switch to a LHRH analogue after registration.
  • Patients must have one of the following a) Low volume disease (defined as no visceral metastases and < 4 bone metastases) or b) are not candidates for docetaxel based chemotherapy or 3) refused docetaxel chemotherapy

Who cannot join

  • History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma) at any time in the past. Also, history of loss of consciousness or transient ischemic attack within 12 months of Day 1 visit;
  • Known or suspected brain metastasis or active leptomeningeal disease;
  • Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment;
  • Absolute neutrophil count < 1,000/μL, or platelet count < 50,000/μL, or hemoglobin<8 g/dL) at the Screening visit.
  • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal
  • Creatinine > 177 μmol/L (2 mg/dL)
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  • Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure (NYHA) class 3 or 4 in the past, unless screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is greater or equal to 45%; History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes); History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit; Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG; Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
  • Treatment with concurrent 5-α reductase inhibitors (finasteride, dutasteride), estrogens, and/or cyproterone
  • Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumor activity within 4 weeks of enrollment (Day 1 visit);
  • History of prostate cancer progression on ketoconazole;
  • Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or agents that block the androgen receptor (e.g.,ARN-509)
  • Previous enzalutamide therapy;
  • Use of an investigational agent within 2 weeks of enrollment (Day 1 visit);
  • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of replacement steroids or > equivalent of 10 mg of prednisone per day within 4 weeks of enrollment (Day 1 visit);
  • Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.
  • Prior chemotherapy for metastatic disease.
  • >30 days of antiandrogen therapy monotherapy without androgen deprivation therapy.
  • Life expectancy of 6 months or less.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

Other trials in United States

About this study

Official title: Randomized Phase II Screening Trial of Enzalutamide/MDV-3100 and LHRH Analogue vs Combined Androgen Deprivation (LHRH Analogue + Bicalutamide) in Metastatic Hormone Sensitive Prostate Cancer

This randomized phase II trial studies if enzalutamide added to standard luteinizing hormone-releasing hormone (LHRH) analogue therapy will improve effects against prostate cancer compared to the standard therapy of LHRH analogue and bicalutamide. Hormone therapies stop the body from producing or block the effect of male sex hormones (testosterone). Enzalutamide blocks the effect of male sex hormones which are responsible for the growth of prostate cancer. Hormonal therapies that lower the level of testosterone are among the most effective treatments for prostate cancer that have spread to other areas of the body (metastasized). It is not yet known whether LHRH analogue therapy with bicalutamide is more effective than LHRH analogue therapy with enzalutamide in treating prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the rates of achieving prostate-specific antigen (PSA) remission at month 7 with LHRH analogue therapy and enzalutamide (Arm A) with that achieved with LHRH analogue and bicalutamide (Arm B) in metastatic hormone sensitive prostate cancer.

SECONDARY OBJECTIVES:

  1. To compare the primary endpoint by race. II. To compare the rates of each of 2 types of response by treatment arm: measurable disease response; and PSA response.

III. To compare each of 7 time-to-event endpoints by treatment arm: duration of overall response (RD); duration of stable disease (SDD); time to treatment failure (TTF); time-to-progression (TTP); TTP in patients with bone metastases; progression-free survival (PFS); and overall survival (OS).

IV. To compare the rates of each type of toxicity by treatment arm. V. To compare the incidence rate of skeletal related events (SRE), and the time until SRE, separately by treatment arm.

VI. To compare the rates of circulating tumor cell (CTC) response by treatment arm.

VIII. To explore the molecular mechanisms within the androgen receptor pathway by determining the levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) expression, androgen metabolism enzymes; androgen receptor variants, and length of cytosine-adenine-guanine (CAG) repeats within the androgen receptor gene, and to associate them with the primary endpoint.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive enzalutamide orally (PO) once daily (QD) and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other Food and Drug Administration [FDA] approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
enzalutamide, bicalutamide, orchiectomy, leuprolide acetate, goserelin acetate
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • enzalutamideDrug

    Also called MDV3100, selective androgen receptor modulator MDV3100, XTANDI

    Given PO

  • bicalutamideDrug

    Also called Casodex, CDX

    Given PO

  • orchiectomyProcedure or surgery

    Undergo orchiectomy or receive LHRH analogue therapy

  • leuprolide acetateDrug

    Also called Enantone, LEUP, Lupron, Lupron Depot

    Undergo orchiectomy or receive LHRH analogue therapy

  • goserelin acetateDrug

    Also called ICI-118630, ZDX, Zoladex

    Undergo orchiectomy or receive LHRH analogue therapy

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02058706
Study groupRoleWhat they receive
Arm A (enzalutamide and LHRH analogue therapy)ExperimentalPatients receive enzalutamide orally PO QD and undergo orchiectomy or receive LHRH analogue therapy (leuprolide acetate, goserelin acetate, or any other FDA approved preparation). Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: enzalutamide; Procedure: orchiectomy; Drug: leuprolide acetate; Drug: goserelin acetate; Other: laboratory biomarker analysis
Arm B (bicalutamide and LHRH analogue therapy)Active comparatorPatients receive bicalutamide PO QD and undergo orchiectomy or receive LHRH analogue therapy as in Arm A. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Drug: bicalutamide; Procedure: orchiectomy; Drug: leuprolide acetate; Drug: goserelin acetate; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria

    Number of Participants with PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria specifically at the 7 month time point. The binary endpoint (yes/no) will be summarized with its point estimate (an occurrence rate), and 2-sided Wilson type 95% confidence interval (CI). PSA response rates will be compared by treatment arm in a stratified logistic regression model.

    Measured: Month 7

Secondary outcomes (9)

  1. Achievement of Measurable Disease Response

    The number of participants with Measurable disease response per RECIST v1.1.

    Measured: Up to 2 years

  2. Achievement of PSA Response Assessed Using PCWG2 Criteria

    Will be summarized with point estimates (occurrence rates), and 2-sided Wilson type 95% CIs.

    Measured: Up to 2 years

  3. The Percentage of Patients Responding

    Point estimates will be calculated and CI estimates will be derived from the Wilcoxon method using STATA software.

    Measured: 6 months

  4. Time to Treatment Failure

    Time to Treatment Failure from date of first treatment to date off treatment or date patient is taken off study for any reason. TTF will be estimated with standard K-M methodology. Point and CI estimates of the median and various time point-specific rates will be derived from the K-M life table.

    Measured: Assessed up to 6 years.

  5. Percentage of Patients Progression Free at One Year

    Percentage of patients progression free at one year using the Kaplan-Meier method.

    Measured: assessed at 1 year

  6. Percentage of Patients With Bone Metastases Progression Free at Six Months

    Percentage of patients with bone metastases Progression free at six months using the Kaplan-Meier method.

    Measured: assessed at six months

  7. Percentage of Patients Progression-free at 6 Months

    Will be estimated with standard K-M methodology. Point and CI estimates of the six-month rate will be derived from the K-M life table.

    Measured: From registration to PSA progression defined by PCWG II criteria or measurable disease by RECIST 1.1, assessed at 6 months

  8. Overall Survival at 2 Years

    Overall Survival will be measured from date of registration to death or last follow up. OS will be estimated with standard K-M methodology. Point and CI estimates of the 2-year rate will derived from the K-M life table.

    Measured: Assessed at 2 years

  9. The Number of Participants With a CTC Response

    Will be summarized with point estimates (occurrence rates). A CTC response is defined as any level of CTC < 5 that is maintained or any level of CTC that is reduced from baseline.

    Measured: Up to month 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2014 (estimated)
  2. Study startMay 2014
  3. Primary completion1 Mar 2021
  4. Study completion1 Mar 2021

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02058706
Sponsor's protocol ID
2013-083
Other IDs
NCI-2014-00212, 2013-083, P30CA022453
Status last verified
May 2023
First submitted
6 Feb 2014
Last updated
10 May 2023
Data monitoring committee
Yes

Publications

  • Vaishampayan UN, Heilbrun LK, Monk P 3rd, Tejwani S, Sonpavde G, Hwang C, Smith D, Jasti P, Dobson K, Dickow B, Heath EI, Semaan L, Cher ML, Fontana JA, Chinni S. Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2034633. doi: 10.1001/jamanetworkopen.2020.34633.

    PubMed 33496795

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing enzalutamide, bicalutamide and orchiectomy in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by Barbara Ann Karmanos Cancer Institute at 4 sites in United States.

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 14 inclusion and 19 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: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With PSA Remission Assessed Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria (time frame: Month 7). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02058706, which also lists 1 linked publication.

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 10 May 2023.

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