Hormone Therapy and Docetaxel before Surgery and Radiation Therapy in Treating Patients with Newly Diagnosed Oligometastatic Prostate Cancer

This phase II trial studies the side effects of hormone therapy and docetaxel before surgery and radiation therapy in treating patients with newly diagnosed prostate cancer that has spread from the primary tumor through the body to form a small number of new tumors in one or two other parts of the body. Androgens are a type of hormone that can cause the growth of prostate cancer cells. Androgen deprivation therapy, stops the growth of tumor cells by lessening the amount of androgens made by the body. Drugs used in 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. Giving androgen deprivation therapy and chemotherapy before radical prostatectomy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving radiation therapy after surgery may kill any remaining tumor cells. Stereotactic body radiation therapy (SBRT) 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 and chemotherapy before surgery and SBRT may work better in treating patients with newly diagnosed oligometastatic prostate cancer.

Inclusion Criteria

• Willing and able to provide written informed consent
• 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 (~24 weeks) of neoadjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions; additionally, must be willing to be treated with a full year 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)
• Able to swallow the study drugs whole as tablets

Exclusion Criteria

• Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
• Prior therapy to a metastatic site
• Prior 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. abiraterone, enzalutamide) * Immunotherapy (e.g. sipuleucel-T, ipilimumab) * Chemotherapy (e.g. docetaxel, cabazitaxel) * Note: may be enrolled if hormone therapy was recently initiated of any kind (< 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
• Ongoing systemic therapy for prostate cancer including, but not limited to: * Immunotherapy (e.g. sipuleucel-T, ipilimumab) * Non-protocol prescribed chemotherapy (e.g. cabazitaxel)
• 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 upper limit of normal
• 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 safety of the following therapy: (1st) systemic chemo-hormonal therapy with 6-cycles (~24 weeks) of neoadjuvant androgen deprivation and chemotherapy, (2nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and then (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 [QLQ]-core 30 [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 program (SEER) database.

OUTLINE:

NEOADJUVANT TREATMENT: Patients receive leuprolide acetate intramuscularly (IM) or subcutaneously (SC) every 3 months for up to 6 months. Patients also receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

LOCAL CONSOLIDATION: 1.5 months after final course of chemotherapy, patients undergo radical prostatectomy. Beginning 3 months after surgery, patients may undergo radiation therapy over 3 weeks. Beginning 2-3 months after surgery, patients undergo SBRT to metastatic sites in 1-5 weeks.

SYSTEMIC CONSOLIDATION: Patients continue to receive leuprolide acetate IM or SC every 3 months for 1 year.

After completion of study treatment, patients are followed up every 3-6 months for 36 months.

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Kenneth James Pienta

Primary ID J1618
Secondary IDs NCI-2016-00836, IRB00070003, CRMS-63459
Clinicaltrials.gov ID NCT02716974