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Summary

for males ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

This randomized phase III trial studies enzalutamide to see how well it works compared to enzalutamide, abiraterone, and prednisone in treating patients with castration-resistant metastatic prostate cancer. Androgens can cause the growth of prostate cancer cells. Drugs, such as enzalutamide, abiraterone acetate, and prednisone, may lessen the amount of androgens made by the body.

Official Title

Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer

Details

Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide, abiraterone and prednisone. Treatment will continue until disease progression or unacceptable toxicity. Patients are followed for clinical outcomes for a maximum of 5 years post study treatment. The primary and secondary objectives are described below.

  1. Primary Objective:

To compare the overall survival of patients with progressive metastatic castration-resistant prostate cancer (CRPC) treated with either enzalutamide only or enzalutamide with abiraterone and prednisone

  1. Secondary Objectives:
  2. To assess the grade 3 or higher toxicity profile and compare safety by treatment arm.
  3. To assess and compare post-treatment prostate-specific antigen (PSA) declines by treatment arm.
  4. To compare radiographic progression free survival defined by Prostate Cancer Working Group 2 (PCWG2), and objective response rate, by treatment arm.
  5. To test for radiographic progression free survival (rPFS) treatment interaction in predicting overall survival.
  6. To assess pre- and post-treatment measures of tumor burden and bone activity using sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and technetium (Tc) methylene diphosphonate (MDP) bone scintigraphy and correlate these measures with overall survival.
  7. To develop and validate prognostic and predictive models of overall survival that include baseline clinical and molecular markers.

Keywords

Adenocarcinoma of the Prostate Hormone-resistant Prostate Cancer Recurrent Prostate Cancer Stage IV Prostate Cancer Prednisone

Eligibility

For males ages 18 years and up

Eligibility Criteria:

  1. Documentation of Disease - Progressive castration-resistant metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  2. Patients must have measurable or non-measurable disease:
  3. Measurable Disease - For visceral or extra nodal lesions to be considered measurable, they must be ≥ 10 mm in one dimension, using spiral CT. For lymph nodes to be considered measurable (ie, target or evaluable lesions), they must be≥ 20 mm in at least one dimension, using spiral CT.
  4. Non-Measurable Disease - All other lesions, including small lesions (longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and truly non-measurable lesions. Lesions that are considered non-measurable include bone lesions (only).
  5. Patients with node only disease (ie, no presence of visceral, extra nodal lesions or bone lesions) must have node(s) that measure ≥ 15 mm in short axis.
  6. Progressive Disease - Patients must have progressive disease at study entry defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy. For patients enrolling on the basis of soft tissue or bone progression, the baseline scan must show progression relative to a comparison scan. If the comparison scan is not available, the baseline scan report must reference the previous scan to document progression.
  7. PSA progression defined by a minimum of two rising PSA levels with an interval of≥ 1 week between each determination. Patients who received an anti-androgen must have progression documented by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination such that at least the second of these rises is ≥ 4 weeks since last flutamide, bicalutamide or nilutamide.

The PSA value at the screening should be ≥ 2 µg/L (2 ng/mL) .

  1. Soft tissue disease progression defined by the protocol
  2. Bone disease progression defined by the Prostate Cancer Working Group 2 (PCWG2)with two or more new lesions on bone scan
  3. Prior Treatment
  4. No treatment with prior taxane-based chemotherapy for metastatic disease
  5. Patients who received prior taxane-based chemotherapy as neoadjuvant or adjuvant therapy for local disease, or who received taxane-based therapy in the PSA clinical (non-metastatic) state is allowable provided that the total duration of exposure was six cycles or less and chemotherapy was completed more than 6 months prior to registration
  6. Taxane-based chemotherapy that was aborted due to allergic reactions or intolerance to chemotherapy and therefore received one cycle of prior therapy is allowable
  7. No prior enzalutamide, abiraterone or other novel antiandrogen or androgen synthesis inhibitor
  8. No treatment with any of the following for prostate cancer within 4 weeks prior to enrollment:
  9. Hormonal therapy (e.g., androgen receptor [AR] antagonists, 5 alpha reductase inhibitors, estrogens) Note: Treatment with bicalutamide and nilutamide within 4 weeks prior to enrollment is not allowed. Treatment with flutamide within 4 weeks prior to enrollment is not allowed. Treatment with all other gonadotropin- releasing hormone (GnRH) analogues or antagonists is allowed.
  10. Chemotherapy
  11. Biologic therapy
  12. Investigational therapy
  13. Immunotherapy
  14. No use of herbal products that may decrease PSA levels within 4 weeks prior to enrollment
  15. No use of systemic steroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks prior to enrollment
  16. No prior use of ketoconazole for greater than 7 days
  17. No prior radiation therapy or radionuclide therapy for the treatment of metastasis within four weeks prior to enrollment
  18. Patients receiving bisphosphonate therapy or denosumab must have been on a stable dose for at least 4 weeks prior to enrollment
  19. Patients must maintain ongoing androgen deprivation therapy with a GnRH analogue,antagonist, or bilateral orchiectomy (i.e., surgical or medical castration)
  20. Patient History
  21. No known or suspected brain metastases (NOTE: patients with treated epidural disease are allowed)
  22. No planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
  23. No structurally unstable bone lesions suggesting impending fracture
  24. No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma). No history of transient ischemic attack (TIA) within 12 months of enrollment
  25. No clinically significant cardiovascular disease including:
  26. Myocardial infarction (MI) within 6 months
  27. Uncontrolled angina within 3 months
  28. Congestive heart failure (CHF) with New York Heart Association (NYHA) class 3 or 4, or patients with NYHA class 3 or 4 in the past, unless a screening echocardiogram (echo) or multigated acquisition scan (MUGA) performed within three months demonstrates an ejection fraction (EF) > 45%
  29. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  30. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
  31. Hypotension (systolic blood pressure [BP] < 86 mmHg) or bradycardia (< 50 bpm) at screening
  32. Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg at screening)
  33. No gastrointestinal (GI) disorder that negatively affects absorption
  34. No major surgery within 4 weeks prior to enrollment
  35. Age and performance status
  36. Age ≥ 18 years of age
  37. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  38. Asymptomatic or mildly symptomatic from prostate cancer
  39. Required Initial Laboratory Values
  40. Granulocytes ≥ 1,500/µL
  41. Platelet count ≥ 100,000/µL
  42. Hemoglobin ≥ 9 g/dL
  43. Creatinine ≤ 2 x upper limits of normal (ULN)
  44. Bilirubin ≤ 1.5 x ULN
  45. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 x ULN
  46. Albumin ≥ 3 g/dl
  47. Total testosterone ≤ 50 ng/dL (1.7 nmol/L)

Locations

  • University Oncology Associates
    Fresno, California, 93701, United States
  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, United States
  • Veterans Affairs Medical Center - San Francisco
    San Francisco, California, 94121, United States
  • California Cancer Center - North Fresno
    Fresno, California, 93720, United States
  • Kaiser Permanente
    Fresno, California, 93720, United States
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Marin Cancer Care Inc
    Greenbrae, California, 94904, United States
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, United States
  • Kaiser Permanente-Oakland
    Oakland, California, 94611, United States
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, United States
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, United States
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, United States
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, United States
  • Kaiser Permanente-Fremont
    Fremont, California, 94538, United States
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, 94086, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, United States
  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California, 94531, United States
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, United States
  • Saint Helena Hospital
    Saint Helena, California, 94574, United States
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, United States
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, United States
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, United States
  • Saint Joseph's Medical Center
    Stockton, California, 95204, United States
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, United States
  • Kaiser Permanente-South Sacramento
    Sacramento, California, 95823, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Kaiser Permanente-Modesto
    Modesto, California, 95356, United States
  • Kaiser Permanente - Sacramento
    Sacramento, California, 95825, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, United States
  • Fremont - Rideout Cancer Center
    Marysville, California, 95901, United States
  • Feather River Cancer Center
    Paradise, California, 95969, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California, 91402, United States
  • Kaiser Permanente
    Woodland Hills, California, 91367, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California, 91505, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, United States
  • Kaiser Permanente-Cadillac
    Los Angeles, California, 90034, United States
  • Los Angeles County-USC Medical Center
    Los Angeles, California, 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, United States
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California, 91706, United States
  • Kaiser Permanente-Bellflower
    Bellflower, California, 90706, United States
  • Kaiser Permanente - Harbor City
    Harbor City, California, 90710, United States
  • Kaiser Permanente Hospital
    Fontana, California, 92335, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California, 92807, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, 92868, United States
  • Kaiser Permanente-Riverside
    Riverside, California, 92505, United States
  • Loma Linda University Medical Center
    Loma Linda, California, 92354, United States
  • USC Norris Oncology/Hematology-Newport Beach
    Newport Beach, California, 92663, United States
  • Kaiser Permanente-Irvine
    Irvine, California, 92618, United States
  • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    Las Vegas, Nevada, 89128, United States
  • Comprehensive Cancer Centers of Nevada
    Las Vegas, Nevada, 89148, United States
  • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    Las Vegas, Nevada, 89113, United States
  • Comprehensive Cancer Centers of Nevada - Central Valley
    Las Vegas, Nevada, 89169, United States
  • Kaiser Permanente-San Marcos
    San Marcos, California, 92069, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT01949337
Phase
Phase 3
Lead Scientist
Terence Friedlander
Study Type
Interventional
Last Updated
March 1, 2017