A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Leuprolide Acetate
- Conditions
- Prostate Cancer
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 26
- Locations
- 3
- Primary Endpoint
- Efficacy as Assessed by 2-year PSA Progression-free Survival Rate
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed 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.
Investigators
Eligibility Criteria
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:
- •Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
- •Cytochrome (CYP) -17 inhibitors (e.g. ketoconazole)
- •Antiandrogens (e.g. bicalutamide, nilutamide)
- •Second generation antiandrogens (e.g. enzalutamide, abiraterone)
- •Immunotherapy (e.g. sipuleucel-T, ipilimumab)
- •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.
Arms & Interventions
chemohormonal and definitive therapy
(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.
Intervention: Leuprolide Acetate
chemohormonal and definitive therapy
(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.
Intervention: Bicalutamide
chemohormonal and definitive therapy
(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.
Intervention: Docetaxel
chemohormonal and definitive therapy
(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.
Intervention: Prostatectomy
chemohormonal and definitive therapy
(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.
Intervention: Radiation
Outcomes
Primary Outcomes
Efficacy as Assessed by 2-year PSA Progression-free Survival Rate
Time Frame: 2 years
To evaluate efficacy of multimodality therapy in men, defined as the 2 year PSA progression-free (PSA\<0.2 ng/ml) survival among men who have non-castrate testosterone levels 2 years after enrollment. Number of participants (who have non-castrate testosterone levels 2 years after enrollment) with PSA progression-free survival.
Secondary Outcomes
- Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities(3 years)
- Time to Prostate-specific Antigen Recurrence(3 years)