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Trial of Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02508636
Recruitment Status : Completed
First Posted : July 27, 2015
Last Update Posted : September 28, 2020
National Comprehensive Cancer Network
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This is a phase II study to evaluate efficacy, safety, toxicity, and feasibility of the addition of enzalutamide to leuprolide for a total duration of 24 months in patients with very high-risk prostate cancer or pelvic node positive disease receiving radiotherapy. Very high-risk prostate cancer is defined as 2 or more of the following characteristics: 1) cT3a/b, 2) PSA ≥20 and <150, 3) Gleason 8-10, and 4) ≥33% core involvement.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Pelvic Nodal Drug: Enzalutamide Drug: Leuprolide Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Definitive Radiotherapy With Leuprolide and Enzalutamide in High Risk Prostate Cancer
Actual Study Start Date : December 22, 2015
Actual Primary Completion Date : August 31, 2020
Actual Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Single Arm

Enzalutamide: 160 mg (for 40 mg capsules) per day; Oral - swallow capsules hole, with or without food; Enzalutamide therapy to begin within 0-7 days of the date of the first Luteinizing Hormone-Releasing Hormone (LHRH) agonist administration for total duration of 24 months.

Leuprolide: any duration formulation: single 7.5mg injection every month; single 22.5 mg injection every 3 months; single 30mg injection every 4 months; single 45 mg injection every 6-months based on the manufacturer for a total of 24 months; Intramuscular injection

Drug: Enzalutamide
Other Name: Xtandi

Drug: Leuprolide
Other Name: Lupron Depot

Primary Outcome Measures :
  1. Rate of acute treatment-related toxicity [ Time Frame: ≤ 90 days within the completion of radiotherapy ]
    Percentage of participants with acute, treatment-related toxicity (≤90 days within the completion of radiotherapy) for any treatment-related adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  2. Rate of late treatment-related toxicity [ Time Frame: Up to 3 years ]
    Percentage of participants with late, treatment-related, toxicity is defined as any toxicity occurring >= 90 days from completion of radiotherapy for any treatment-related adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients will be monitored at least weekly during treatment and every 3-6 months up to 24 months and at 36 months after radiation therapy.

  3. Prostate Specific Antigen-Complete Response (PSA-CR) Rate [ Time Frame: Up to 127 days ]
    A PSA measurement will be obtained at 120-127 days after initiation of androgen deprivation therapy. The proportion of patients achieving a PSA-CR (PSA nadir ≤0.3) at 120-127 days will be determined. The historical proportion of patients (0.7) attaining a PSA-CR from Radiation Therapy Oncology Group (RTOG) 9413 will be utilized for comparison.

Secondary Outcome Measures :
  1. Time to biochemical failure [ Time Frame: Up to 3 years ]
    ≥2 ng/mL from the nadir PSA per the Phoenix Definition

  2. Local progression [ Time Frame: Up to 3 years ]
    Biopsy proven recurrence

  3. Regional progression [ Time Frame: Up to 3 years ]
    Imaging or biopsy

  4. Distant progression [ Time Frame: Up to 3 years ]
    Imaging or biopsy

  5. Time to clinical progression [ Time Frame: Up to 3 years ]
    Date of PSA failure, local failure, regional or distant metastases

  6. Changes in hemoglobin A1c (HbA1c) levels during treatment [ Time Frame: Up to 2 years ]
    Changes in HbA1c will be assessed at baseline, 12, and 24 months during treatment

  7. Changes in fasting insulin levels during treatment [ Time Frame: Up to 2 years ]
    Changes in fasting insulin will be assessed at will be assessed at baseline, 12, and 24 months during treatment

  8. Changes in fasting glucose levels during treatment [ Time Frame: Up to 2 years ]
    Changes in fasting glucose will be assessed at baseline, 12, and 24 months during treatment

  9. Changes in lipid and cholesterol levels during treatment [ Time Frame: Up to 2 years ]
    Changes in fasting lipid and cholesterol levels will be assessed at baseline, 12, and 24 months during treatment

  10. Expanded Prostate Cancer Index Composite (EPIC) [ Time Frame: up to 3 years ]
    The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment and assesses the disease-specific aspects of prostate cancer and its therapies and comprises four summary domains (Urinary, Bowel, Sexual and Hormonal). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life

  11. Patient-Reported Outcomes Measurement Information System (PROMIS) [ Time Frame: up to 3 years ]
    PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. A PROMIS score of 50 is the average (or mean) score for a specific, relevant group of people under investigation. That group is the reference population. The PROMIS measures the responses use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. A score of 40 is one SD lower than the mean of the reference population and a score of 60 is one SD higher than the mean of the reference population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). Thus a score of 60 is one standard deviation above the average referenced population. This could be a desirable or undesirable outcome, depending upon the concept being measured.

  12. EuroQol Group five dimensional questionnaire (EQ-5D) [ Time Frame: up to 3 years ]
    EQ-5D is a standardized instrument for measuring generic health status. The health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". In pain/discomfort dimension, it asks how much pain or discomfort they have, and in anxiety/depression dimension, it asks how anxious or depressed they are. The respondents self-rate their level of severity for each dimension using three-level (EQ-5D-3L) or five-level (EQ-5D-5L) scale, with lower levels indicating less issues/problems with that particular health dimension.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to registration at very high risk of recurrence as determined by 2 or more of the following combinations:

    • cT3a/b
    • PSA ≥20
    • Gleason score 8-10
    • ≥33% core involvement OR any patient with pelvic lymph node involvement ≥1cm as determined by pelvic CT or MRI imaging will meet eligibility criteria for enrollment.
  2. Standard staging exams for patients with high-risk prostate cancer including bone scan or NaF Positron Emission Tomography (PET) /CT scan, and pelvic and prostate MRI.
  3. No distant metastases (M0) on bone scan or NaF PET/CT within 90 days prior to registration. Equivocal bone scan findings are allowed if the physician determines that distant metastases are unlikely based on clinical judgment.
  4. Zubrod Performance Status 0-2 within 60 days prior to enrollment.
  5. Age ≥18
  6. Complete blood count (CBC) with differential obtained within 30 days prior to registration on study, with adequate bone marrow function defined as follows:

    1. Absolute neutrophil count (ANC) ≥1,800 cells/mm3
    2. Platelets ≥100,000 cells/mm3
    3. Hemoglobin ≥8.0 g/dl (The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
    4. Serum creatinine <2.0 mg/dl and creatinine clearance >40 mL/min within 30 days prior to registration
    5. Bilirubin <1.5 x ULN and Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) <2 × ULN within 21 days prior to registration
  7. Patients, even if surgically sterilized (i.e., status post vasectomy), who:

    1. Agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug, or
    2. Agree to completely abstain from intercourse
  8. Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria:

  1. Definite evidence of metastatic disease
  2. Prior radical prostatectomy or bilateral orchiectomy for any reason
  3. Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.
  4. Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).
  5. Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields.
  6. Previous hormonal therapy such as LHRH agonists (e.g. goserelin, leuprolide), anti-androgens (e.g. flutamide, bicalutamide), estrogens (e.g. DES), or surgical castration (orchiectomy)
  7. Known hypersensitivity to enzalutamide or related compounds
  8. History of adrenal insufficiency
  9. Patients who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  10. Prior allergic reaction to the drugs involved in this protocol.
  11. Cushing's syndrome
  12. Severe chronic renal disease (serum creatinine >2.0 mg/dl and confirmed by creatinine clearance <40 mL/minute)
  13. Chronic liver disease (bilirubin >1.5x ULN, ALT or AST >2x ULN)
  14. Active/Uncontrolled Viral Hepatitis
  15. Chronic treatment with glucocorticoids within one year.
  16. History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with antiepileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization.
  17. Clinically significant cardiovascular disease including:

    1. Myocardial infarction within 6 months prior to screening
    2. Uncontrolled angina within 3 months prior to screening
    3. Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months results in a left ventricular ejection fraction that is ≥45%;
    4. History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes);
    5. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
    6. Uncontrolled hypertension as indicated by a resting systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg at screening. Patients with initially elevated systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg are eligible if they undergo medical management and are re-screened.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02508636

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United States, California
University of California San Francisco
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
National Comprehensive Cancer Network
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Principal Investigator: Hao Nguyen, MD University of California, San Francisco
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Responsible Party: University of California, San Francisco Identifier: NCT02508636    
Other Study ID Numbers: 15558
NCI-2015-01757 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: July 27, 2015    Key Record Dates
Last Update Posted: September 28, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents