Hormone Therapy and Radiation Therapy in Treating Patients with Non-metastatic, Intermediate, or High Risk Prostate Cancer

Status: Active

Description

This early phase I trial studies the best dose of radiation therapy when given together with standard hormone therapy and to see how well they work in treating men with prostate cancer that has not spread to other places in the body or that is likely to come back. Androgens can cause the growth of prostate cancer cells. Drugs, such as bicalutamide, dutasteride and finasteride, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving hormone therapy together with radiation therapy may be a better treatment for prostate cancer while improving health-related quality of life.

Eligibility Criteria

Inclusion Criteria

  • Age >= 70 years AND/OR Charlson comorbidity index score >= 2 (prostate cancer diagnosis does not contribute to total score)
  • Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma
  • Intermediate or high risk for recurrence according to the following criteria: * Two or more of the following intermediate risk features for recurrence ** Gleason score = 7 ** Prostate-specific antigen (PSA) 10-20 ng/ml ** Clinical stage T2b-T2c ** Percent positive biopsy cores >= 50% OR * One or more of the following high risk features for recurrence ** Gleason score 8-10 ** PSA > 20 ng/ml ** Clinical stage T3a-T4
  • Clinically negative lymph nodes as established by imaging (pelvic +/- abdominal computed tomography [CT] or magnetic resonance imaging [MRI]), nodal sampling, or dissection, except as noted immediately below: * Patients with intermediate risk factors only do not require abdominopelvic imaging, but these studies may be obtained at the discretion of the treating physician * For men with any high risk feature (PSA > 20, Gleason score > 8, or clinical stage T3), a pelvic CT or MRI, are required; it is recommended that the duration between these scans and study registration be less than 60 days, but if the time period is > 60 days and the opinion of the clinician is that repeat studies would offer limited benefit, then these studies do not need to be repeated; a lymph node will be considered radiographically positive if it is > 1.5 cm in size, occurs within the expected distribution for prostate cancer metastasis (i.e. internal iliac or obturator fossa), and is without classic benign features (i.e. fatty hilum); patients with lymph nodes equivocal or questionable by imaging are eligible for inclusion in this study
  • No evidence of bone metastases (M0) on bone scan * Patients with intermediate risk factors only do not require a bone scan, but these studies may be obtained at the discretion of the treating physician * Patients with any high risk factors are required to undergo a bone scan; it is recommended that the duration between these scans and study registration be less than 60 days, but if the time period is > 60 days and the opinion of the clinician is that repeat studies would offer limited benefit, then these studies do not need to be repeated * Equivocal bone scan findings are allowed if additional imaging (e.g. plain film x-rays, or CT) does not confirm metastasis
  • History/physical examination to include, at a minimum, digital rectal examination of the prostate and examination of the skeletal system and abdomen, and formal comorbidity assessment via the Charlson Comorbidity Index within 60 days prior to registration
  • Zubrod performance status 0-2
  • Baseline serum PSA value performed with a Food and Drug Administration (FDA)-approved assay (e.g., Abbott, Hybritech) within 60 days prior to registration
  • Baseline serum testosterone obtained within 60 days prior to registration
  • Study entry PSA and serum testosterone must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of oral androgen manipulation; (3) within 30 days after discontinuation of finasteride or dutasteride
  • Absolute neutrophil count (ANC) >= 1,800 cells/mm^3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
  • Patient must be able to provide study-specific informed consent prior to study entry
  • Total bilirubin =< 2 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

Exclusion Criteria

  • Prior radical surgery (prostatectomy), high-intensity focused ultrasound (HIFU) or cryosurgery for prostate cancer
  • Prior hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol [DES]), or bilateral orchiectomy
  • Use of 5-alpha reductase inhibitors (finasteride, dutasteride) specifically prescribed for the treatment of prostate cancer
  • Prior or concurrent cytotoxic chemotherapy for prostate cancer; prior chemotherapy for a different cancer is permitted
  • Prior radiation, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy (RT) fields
  • Active lupus or scleroderma
  • Severe, active co-morbidity, including but not limited to: * Unstable angina within the last 6 months without subsequent corrective cardiovascular procedure * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Hepatic insufficiency with AST, ALT, or bilirubin > 2 x upper limit of normal, clinical jaundice, and/or coagulation defects * Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; patients who are HIV seropositive but do not meet criteria for diagnosis of AIDS are eligible for study participation

Locations & Contacts

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Stanley Lawrence Liauw
Phone: 773-702-6870
Email: sliauw@radonc.uchicago.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To test the hypothesis that health-related quality of life (HRQOL) in patients treated with dual oral androgen manipulation will be improved compared to that of controls treated with standard androgen deprivation therapy (ADT) including a gonadotropin releasing hormone (GnRH) agonist +/- an antiandrogen.

SECONDARY OBJECTIVES:

I. To test the hypothesis that oncologic outcomes including biochemical progression free survival, distant metastasis free survival, cause specific survival, and overall survival after treatment with dual oral androgen manipulation and dose escalated radiation will be comparable to the outcomes of patients treated with standard ADT.

TERTIARY OBJECTIVES:

I. Analyze the ribonucleic acid (RNA) expression of prostate cancers treated with hormonal therapy prior to radiation for prostate cancer.

II. Compare differences in expression across the 2 cohorts of patients, treated with oral-only ADT and traditional injectable ADT.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: This is a dose-escalation study of radiation therapy.

Patients receive bicalutamide orally (PO) daily and dutasteride PO daily or finasteride PO daily for 4 months. After 8 weeks, patients also undergo radiation therapy on 5 days a week (Monday-Friday) for 7-8 weeks. Following completion of radiation therapy, patients continue dutasteride PO daily or finasteride PO daily for 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ADT and standard dose radiation therapy per standard of care.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Trial Phase & Type

Trial Phase

No phase specified

Trial Type

Treatment

Lead Organization

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Stanley Lawrence Liauw

Trial IDs

Primary ID 10-625-A
Secondary IDs NCI-2015-01652
Clinicaltrials.gov ID NCT01342367