Androgen Deprivation Therapy, Docetaxel, External Beam Radiation Therapy, and Stereotactic Body Radiation Therapy in Treating Patients with Prostate Cancer

This phase II trial studies the side effects of androgen deprivation therapy, docetaxel, external beam radiation therapy, and stereotactic body radiation therapy work in treating patients with prostate cancer. Androgen deprivation therapy, such as leuprolide acetate, triptorelin, degarelix, and bicalutamide may lessen the amount of androgen made by the body. Drugs used in the chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. External beam radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving androgen deprivation therapy, docetaxel, external beam radiation therapy, and stereotactic body radiation therapy may work better in treating patients with prostate cancer.

Inclusion Criteria

• Willing and able to provide written informed consent
• Eastern cooperative group (Eastern Cooperative Oncology Group [ECOG]) performance status =< 2
• Documented histologically confirmed adenocarcinoma of the prostate
• Willing to undergo the following therapy: (1st) systemic chemo-hormonal therapy with up to 6-months (around 24 weeks) of neoadjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions; additionally, must be willing to be treated with a full two years of androgen deprivation
• Oligometastatic prostate cancer: stage T1-4, N0-1 and/or M1a-b (up to 5 metastatic lesions-including bone lesions and non-regional lymph nodes)

Exclusion Criteria

• Prior local non-surgical therapy to treat prostate cancer (e.g. radiation therapy, brachytherapy)
• Prior therapy to a metastatic site
• Prior or ongoing systemic therapy for prostate cancer including, but not limited to: * Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix) * CYP-17 inhibitors (e.g. ketoconazole) * Antiandrogens (e.g. bicalutamide, nilutamide) * Second generation antiandrogens (e.g. enzalutamide, ARN-509) * Immunotherapy (e.g. sipuleucel-T, ipilimumab) * Chemotherapy (e.g. docetaxel, cabazitaxel) * Note: may be enrolled if has recently initiated hormone therapy (< 90 days duration); in the event that hormone therapy was initiated prior to study enrollment, the clock for 1 year of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment
• Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
• Absolute neutrophil count (ANC) < 1500/mm^3
• Platelet count < 100,000/mm^3
• Hemoglobin < 9 g/dL
• Bilirubin > upper limit of normal (ULN)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >= 2.5 x upper limit of normal
• Creatinine clearance of >= 30 mL/min; creatinine clearance (CrCl) should be calculated suing the Cockcroft-Gault formula
• Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six months
• Prior history of malignancy in the past 3 years with the exception of basal cell and squamous cell carcinoma of the skin; other malignancies that are considered to have a low potential to progress may be enrolled at discretion of principal investigator (PI)

PRIMARY OBJECTIVES:

I. To assess the safety of treating men with oligometastatic prostate cancer with the following therapy: (1st) systemic chemo-hormonal therapy with up to 6-months (around 24 weeks) of adjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions.

SECONDARY OBJECTIVES:

I. Two-year undetectable prostate specific antigen (PSA) rate.

II. Time to PSA recurrence.

III. Time to castrate resistant prostate cancer.

IV. Overall survival measured from the start of therapy.

V. Quality of life scoring using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) supplemented with the FACT-Taxane and (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] supplemented with QLQ-PR25).

VI. The time interval from completion of treatment on study until the first chemotherapy.

VII. The time interval from completion of treatment on study until the first androgen deprivation therapy.

VIII. The time interval from completion of treatment on study until any new metastases.

IX. The location of first distant metastatic progression, following completion of treatment on study: visceral versus nodal versus bone.

X. Improved 5-year (yr) overall survival (OS) as compared to 5-yr OS in men with metastatic prostate cancer included in the Surveillance, Epidemiology, and End Results (SEER) database.

OUTLINE:

Patients receive androgen deprivation therapy including leuprolide acetate intramuscularly (IM) or subcutaneously (SC), triptorelin IM, degarelix SC, or bicalutamide orally (PO) daily every 3 months for 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel intravenously (IV) over 1 hour on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Within 1-2 months, patients undergo external beam radiation therapy (EBRT) over 3 weeks. During or right after EBRT, patients then undergo stereotactic body radiation therapy (SBRT) over 1-5 weeks.

After completion of study treatment, patients are followed up every 3 and 6 months for 48 months.

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Kenneth James Pienta

Primary ID J16151
Secondary IDs NCI-2017-01674, IRB00120414, CRMS-65410
Clinicaltrials.gov ID NCT03043807