Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-13239

Full 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 how well enzalutamide with standard luteinizing hormone-releasing hormone (LHRH) analogue therapy work compared to the standard therapy of LHRH analogue and bicalutamide in treating patients with prostate cancer that has spread to other places in the body (metastatic). Androgens are male sex hormones that can cause the growth of prostate cancer cells. Anti-hormone therapy, such as enzalutamide and bicalutamide, block the effect of androgens in prostate tumor cells. LHRH analogue therapy stops the body from making the male sex hormone testosterone. It is not yet known whether enzalutamide with LHRH analogue therapy is more effective than bicalutamide with LHRH analogue therapy in treating patients with metastatic prostate cancer.

Study Objective


I. 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.


I. 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.

Are you eligible?

Inclusion Criteria:

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); no minimum PSA requirement for patients with measurable disease

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 gonadotropin-releasing hormone (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/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

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; computed tomography (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

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 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 c) refused docetaxel chemotherapy

Exclusion Criteria:

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/uL

Platelet count < 50,000/uL

Hemoglobin < 8 g/dL

Total bilirubin > 2.5 times the upper limit of normal

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal

Creatinine > 177 umol/L (2 mg/dL)

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 of 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 >= 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 electrocardiogram (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-alpha 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 of 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 place 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

Genitourinary Cancers Prostate Cancer