A Study of Definitive Therapy to Treat Prostate Cancer

Prostate Cancer Clinical Trial

— oligo-mets  

Official title:

A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02716974
• Other study ID #: J1618
• Secondary ID: IRB00070003
• Status: Completed
• Phase: Phase 2
• Start date: June 2016
• Est. completion date: April 2022

Study information

• Verified date: July 2022
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: April 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Leuprolide Acetate
22.5mg by intramuscular (IM) injection every 3 months
• Bicalutamide
bicalutamide (Casodex) 50mg by mouth daily
• Docetaxel
Docetaxel (taxotere) 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles.

Procedure:
• Prostatectomy
Removal of the entire prostate gland, plus some surrounding tissue.

Radiation:
• Radiation
5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy as Assessed by 2-year PSA Progression-free Survival Rate	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.	2 years
Secondary	Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities	To assess the safety and therapeutic benefit of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer (<5 sites of metastases). Safety is defined as the incidence of Grades 3 and 4 neutropenia and surgical- or radiation-induced toxicities.; Neutropenia is a lower than normal number of neutrophils (a type of white blood cell) in the blood. Although dependent on the specific laboratory, the normal number is of neutrophils is generally about 1500-7800 cells/microliter. Grade 3 and 4 neutropenia refer to neutrophil levels <1,000-500 and <500, respectively. The average risk of docetaxel-induced Grade 3 and 4 neutropenia is about 35%. During the course of the study, if we had seen evidence that the risk of Grade 3 and 4 neutropenia was >50%, the study would have been stopped.	3 years
Secondary	Time to Prostate-specific Antigen Recurrence	To investigate the time from an undetectable prostate-specific antigen (=0.2 ng/mL) until the prostate-specific antigen is >0.2 over two time-points.	3 years