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

NCT02508636 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 15558NCI-2015-01757
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the safety of giving enzalutamide with leuprolide acetate before and after radiation therapy and to see how well it works in treating patients with prostate cancer that is at high risk of returning. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Most types of prostate cancer also need testosterone to grow and spread. After radiation therapy, patients often receive treatments to reduce testosterone to prevent the cancer from returning. Leuprolide acetate works by reducing the amount of testosterone that the body makes. Enzalutamide is a stronger treatment that may block testosterone from reaching cancer cells. Adding enzalutamide to treatment with leuprolide acetate after radiation therapy may help prevent high-risk prostate cancer from returning and improve patient survival.

Conditions

Prostatic Neoplasms; Pelvic Nodal

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Acute Treatment-related Toxicity

  Percentage of participants with acute, treatment-related toxicity defined as \<=90 days within the completion of radiotherapy, for any treatment-related grade 3 or higher adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  From start of treatment to 90 days after completion of radiotherapy, approximately 6 months total

• Percentage of Participants With Late Treatment-related Toxicity

  Percentage of participants with late, treatment-related, toxicity is defined as any toxicity occurring \>= 90 days from completion of radiotherapy for any grade 3 or higher treatment-related adverse events as classified by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  From 90 days after completion of radiotherapy until end of study, approximately 30 months total

• Proportion of Patients Achieving a Prostate Specific Antigen-Complete Response (PSA-CR)

  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.

  Up to 127 days

Secondary Outcomes (15)

• Median Time to Biochemical Failure

  Up to 36 months

• Median Time to Local Failure

  Up to 36 months

• Number of Participants With Regional or Distant Metastases Over Time

  Up to 36 months

• Median Time to Clinical Progression

  Up to 36 months

• Overall Median Change in Hemoglobin A1c (HbA1c) Levels During Treatment

  Up to 24 months

Study Arms (1)

Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy

EXPERIMENTAL

Participants will receive Enzalutamide: 160 mg per day, 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 as well as a single Leuprolide 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. Radiation therapy should begin approximately 8 weeks (+/- 1 week) after the date of the first LHRH agonist/antagonist injection of hormone therapy is given and continue for a total of 5 weeks.

Drug: Enzalutamide; Drug: Leuprolide; Radiation: Intensity-Modulated Radiation Therapy

Interventions

Enzalutamide DRUG

Given orally

Also known as: Xtandi

Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy

Leuprolide DRUG

Given via intramuscular injection

Also known as: Lupron Depot

Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy

Intensity-Modulated Radiation Therapy RADIATION

A total dose of 45 Gy in 25 fractions of 1.8 Gy each.

Also known as: Radiation Therapy, RT

Combination Therapy: Enzalutamide, Leuprolide, Radiotherapy

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• Zubrod Performance Status 0-2 within 60 days prior to enrollment.
• Age ≥18
• Complete blood count (CBC) with differential obtained within 30 days prior to registration on study, with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥1,800 cells/mm3
• Platelets ≥100,000 cells/mm3
• Hemoglobin ≥8.0 g/dl (The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable)
• Serum creatinine \<2.0 mg/dl and creatinine clearance \>40 mL/min within 30 days prior to registration
• Bilirubin \<1.5 x ULN and Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \<2 × ULN within 21 days prior to registration

You may not qualify if:

• Definite evidence of metastatic disease
• Prior radical prostatectomy or bilateral orchiectomy for any reason
• Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.
• Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).
• Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields.
• 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)
• Known hypersensitivity to enzalutamide or related compounds
• History of adrenal insufficiency
• Prior allergic reaction to the drugs involved in this protocol.
• Cushing's syndrome
• Severe chronic renal disease (serum creatinine \>2.0 mg/dl and confirmed by creatinine clearance \<40 mL/minute)
• Chronic liver disease (bilirubin \>1.5x ULN, ALT or AST \>2x ULN)
• Active/Uncontrolled Viral Hepatitis
• Chronic treatment with glucocorticoids within one year.
• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Leuprolide; Radiotherapy, Intensity-Modulated; Radiotherapy

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)

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; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Therapeutics

Limitations and Caveats

The study closed earlier than expected which resulted in a low accrual

Results Point of Contact

• Title: Dr. Hao Nguyen
• Organization: University of California, San Francisco

Hao.Nguyen@ucsf.edu

(415) 514-5541

Study Officials

• Hao Nguyen, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: July 27, 2015
• Study Start: December 22, 2015
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)