A Study of Definitive Therapy to Treat Prostate Cancer After Prostatectomy

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

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 adjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 2 years of androgen deprivation. Androgen blockade will be the same throughout the course of treatment.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Leuprolide Acetate; Drug: Docetaxel; Drug: Bicalutamide; Radiation: Radiation; Drug: Abiraterone Acetate

Detailed Description

Adjuvant 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.

Radiation (month 7 though ~11): After completion of adjuvant chemotherapy, the men will be treated with definitive local therapy with adjuvant radiation therapy (RT). After definitive local therapy, patients will be treated with consolidative stereotactic body radiation therapy (SBRT) to the metastatic sites (if present).

Follow up: Patients will continue on androgen deprivation for a total of 2 years. 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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Johns Hopkins Sibley Memorial Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Age ≥ 18 years
3. Eastern cooperative oncology group (ECOG) performance status ≤2
4. Documented histologically confirmed adenocarcinoma of the prostate
5. 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 adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. Additionally, must be willing to be treated with a full two years of androgen deprivation.
6. 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 PET scan)

Exclusion Criteria:

1. Prior local non-surgical therapy to treat prostate cancer (e.g. radiation therapy, brachytherapy)
2. Prior therapy to a metastatic site.

3. Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

   1. Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)
   2. CYP-17 (cytochrome P450 17α-hydroxy/17,20-lyase) 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 2 years of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment.
4. 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.
5. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
6. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
7. Abnormal liver function (bilirubin >ULN ( upper limit of normal); AST (aspartate aminotransferase), ALT (alanine transaminase) > 2.5 x upper limit of normal)
8. Creatinine clearance of ≥ 30 mL/min. CrCl (Creatinine clearance) should be calculated suing the Cockcroft-Gault formula.
9. Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six months.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: Leuprolide Acetate; 22.5mg by intramuscular (IM) injection every 3 months; Other Names: Lupron Deport; Drug: Docetaxel; 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles. Dose may decreased in the following intervals: 65 mg/M2, 55 mg/M2, 35 mg/M2.; Other Names: Texotere; Drug: Bicalutamide; bicalutamide (Casodex) 50mg by mouth daily; Other Names: Casodex; Radiation: Radiation; Radiation will be delivered in 1 to 5 fractions, and the dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints in accordance with AAPM Task Group 101 recommendations. Typical doses include 16 - 24 Gy in 1 fraction, 48 - 50 Gy in 4 fractions, and 50 - 60 Gy in 5 fractions.; Drug: Abiraterone Acetate; Abiraterone acetate 1000 mg / day may be given at the investigator's discretion.; Other Names: Zytiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate	To evaluate efficacy of multimodality therapy in men, defined as the 3 year Prostate-specific antigen progression-free (Prostate-specific antigen<0.2 ng/ml) survival rate among men who have non-castrate testosterone levels 2 years after enrollment.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification	To assess the safety of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer after prostatectomy. Toxicities related to neoadjuvant therapy, radiation therapy, or stereotactic body radiation therapy (SBRT) will be assessed using CTCAE version 4 criteria. Surgical toxicities will be assessed using the Clavien-Dindo Classification	3 years
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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2017
• Primary Completion (Actual): October 17, 2022
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 3, 2017
• First Posted (Estimate): February 6, 2017

Study Record Updates

• Last Update Posted (Estimate): February 16, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: chemotherapy; radiation; prostatectomy; androgen deprivation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Docetaxel; Leuprolide; Bicalutamide; Abiraterone Acetate
• Other Study ID Numbers: J16151; IRB00120414 (Other Identifier: JHU IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No