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

NCT02058706 | Completed Phase 2 Results DMC

• 3 other identifiers: 2013-083NCI-2014-00212P30CA022453
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (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.

  Month 7

Secondary Outcomes (9)

• Achievement of Measurable Disease Response

  Up to 2 years

• Achievement of PSA Response Assessed Using PCWG2 Criteria

  Up to 2 years

• The Percentage of Patients Responding

  6 months

• Time to Treatment Failure

  Assessed up to 6 years.

• Percentage of Patients Progression Free at One Year

  assessed at 1 year

Study Arms (2)

Arm A (enzalutamide and LHRH analogue therapy)

EXPERIMENTAL

Patients 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.

Drug: enzalutamide; Procedure: orchiectomy; Drug: leuprolide acetate; Drug: goserelin acetate; Other: laboratory biomarker analysis

Arm B (bicalutamide and LHRH analogue therapy)

ACTIVE COMPARATOR

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.

Drug: bicalutamide; Procedure: orchiectomy; Drug: leuprolide acetate; Drug: goserelin acetate; Other: laboratory biomarker analysis

Interventions

enzalutamide DRUG

Given PO

Also known as: MDV3100, selective androgen receptor modulator MDV3100, XTANDI

Arm A (enzalutamide and LHRH analogue therapy)

bicalutamide DRUG

Given PO

Also known as: Casodex, CDX

Arm B (bicalutamide and LHRH analogue therapy)

orchiectomy PROCEDURE

Undergo orchiectomy or receive LHRH analogue therapy

Arm A (enzalutamide and LHRH analogue therapy); Arm B (bicalutamide and LHRH analogue therapy)

leuprolide acetate DRUG

Undergo orchiectomy or receive LHRH analogue therapy

Also known as: Enantone, LEUP, Lupron, Lupron Depot

Arm A (enzalutamide and LHRH analogue therapy); Arm B (bicalutamide and LHRH analogue therapy)

goserelin acetate DRUG

Undergo orchiectomy or receive LHRH analogue therapy

Also known as: ICI-118630, ZDX, Zoladex

Arm A (enzalutamide and LHRH analogue therapy); Arm B (bicalutamide and LHRH analogue therapy)

laboratory biomarker analysis OTHER

Correlative studies

Arm A (enzalutamide and LHRH analogue therapy); Arm B (bicalutamide and LHRH analogue therapy)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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)
• 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);

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 33496795 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; bicalutamide; Orchiectomy; Leuprolide; Goserelin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Castration; Endocrine Surgical Procedures; Surgical Procedures, Operative; Urogenital Surgical Procedures; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Elisabeth Heath
• Organization: Karmanos Cancer Institute

heathe@karmanos.org

313.576.8734

Study Officials

• Elisabeth Heath, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: February 10, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: May 10, 2023
• Results First Posted: May 10, 2023

Record last verified: 2023-05

Locations

US (4)