Clinical trial NCT02716974: A Study of Definitive Therapy to Treat Prostate Cancer
Official title: A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Lupron
Bicalutamide
Docetaxel
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2016-03-23
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Efficacy as Assessed by 2-year PSA Progression-free Survival Rate
timeFrame: 2 years
Secondary outcomes:
measure: Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities
timeFrame: 3 years
measure: Time to Prostate-specific Antigen Recurrence
timeFrame: 3 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: SKCCC at Johns Hopkins University
name: Kenneth Pienta, MD
role: PRINCIPAL_INVESTIGATOR
References: