A Study of Definitive Therapy to Treat Prostate Cancer (oligo-mets)

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: Leuprolide Acetate; Radiation: Radiation; Drug: Docetaxel; Drug: Bicalutamide; Procedure: Prostatectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT02716974

IRB00070003 (Other Identifier)

J1618

Details and patient eligibility

About

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 (~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. The men will receive a total of 1 year of androgen deprivation. Androgen blockade will be the same throughout the course of treatment.

Full description

Neoadjuvant treatment (month 1 through ~6): All patients will be treated with up to 6 months of androgen deprivation, plus up to 6 cycles of docetaxel chemotherapy. Following docetaxel therapy, patients with a prostate-specific antigen response of at least a 50% decrease from baseline, will proceed to maximum consolidative therapy.

Surgery and Radiation (month 7 though ~11): After completion of neoadjuvant therapy, the men will be treated with definitive local therapy with radical prostatectomy (RP) +/- adjuvant radiation therapy (RT). After definitive local therapy, patients will be treated with consolidative stereotactic body radiation therapy (SBRT) to the metastatic sites.

Follow up: Patients will continue on androgen deprivation for a total of 1 year. They will be followed clinically and monitored with serum testosterone and prostate-specific antigen until 2-years after completion of ADT (Androgen deprivation therapy) treatment. Androgen blockade will be the same throughout the course of treatment.

Enrollment: 26 patients

Sex: Male

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Willing and able to provide written informed consent.
• Age ≥ 18 years
• Eastern cooperative 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 seen on bone scan, contrast enhanced CT scan, or positron emission tomography scan)
• 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 or ongoing systemic therapy for prostate cancer including, but not limited to:

  1. Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
  2. Cytochrome (CYP) -17 inhibitors (e.g. ketoconazole)
  3. Antiandrogens (e.g. bicalutamide, nilutamide)
  4. Second generation antiandrogens (e.g. enzalutamide, abiraterone)
  5. Immunotherapy (e.g. sipuleucel-T, ipilimumab)
  6. Chemotherapy (e.g. docetaxel, cabazitaxel) *Note: may be enrolled if hormone therapy was recently initiated (<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.

• Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]

• Abnormal liver function (bilirubin >upper limit of normal; aspartate aminotransferase , alanine aminotransferase > 2.5 x upper limit of normal)

• Creatinine clearance of ≥ 30 mL/min. Creatinine clearance 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 PI.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

chemohormonal and definitive therapy

Experimental group

Description:

(1st) Systemic chemo-hormonal therapy with up to 6-months (\~24 weeks) of neoadjuvant androgen deprivation (Leuprolide Acetate) and up to 6 cycles of chemotherapy (Docetaxel), (2nd) definitive local tumor control with prostatectomy +/- adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 1 year of androgen deprivation. Androgen blockade (Bicalutamide) will be the same throughout the course of treatment.

Treatment:

Procedure: Prostatectomy

Drug: Bicalutamide

Drug: Docetaxel

Radiation: Radiation

Drug: Leuprolide Acetate