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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT02716974
• Collaborator: (none)
• Enrollment: 26
• Locations: 3
• Arm: 1
• Duration (Months): 70
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Leuprolide Acetate; Drug: Bicalutamide; Drug: Docetaxel; Procedure: Prostatectomy; Radiation: Radiation	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Apr 1, 2022
• Actual Study Completion Date: Apr 1, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Leuprolide Acetate; 22.5mg by intramuscular (IM) injection every 3 months; Other Names: Lupron Deport ; Drug: Bicalutamide; bicalutamide (Casodex) 50mg by mouth daily; Other Names: Casodex ; Drug: Docetaxel; Docetaxel (taxotere) 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles.; Other Names: Texotere ; Procedure: Prostatectomy; Removal of the entire prostate gland, plus some surrounding tissue.; Other Names: Radical prostatectomy ; Radiation: Radiation; 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.

Outcome Measures

Primary Outcome Measures

1. Efficacy as Assessed by 2-year PSA Progression-free Survival Rate [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 Outcome Measures

1. Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities [3 years]

   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.

2. Time to Prostate-specific Antigen Recurrence [3 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
2	Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21205
3	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Kenneth Pienta, MD, SKCCC at Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 7, 2020

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02716974
• Other Study ID Numbers: J1618; IRB00070003
• First Posted: Mar 23, 2016
• Last Update Posted: Aug 4, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Lupron; Bicalutamide; Docetaxel
• Additional relevant MeSH terms: Prostatic Neoplasms; Docetaxel; Leuprolide; Bicalutamide

Study Results

Participant Flow

Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
Period Title: Overall Study
STARTED	26
COMPLETED	26
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
Overall Participants	26
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59.8
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	26 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 15.4%
White	22 84.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	26 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy as Assessed by 2-year PSA Progression-free Survival Rate
Description	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.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
Measure Participants	26
Count of Participants [Participants]	17 65.4%

2. Secondary Outcome

Title	Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
Measure Participants	26
Count of Participants [Participants]	26 100%

3. Secondary Outcome

Title	Time to Prostate-specific Antigen Recurrence
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
Measure Participants	26
Median (95% Confidence Interval) [Months]	31

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Chemohormonal and Definitive Therapy
Arm/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. 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. Prostatectomy: Removal of the entire prostate gland, plus some surrounding tissue. Radiation: 5 high dose radiation treatments to the metastatic (tumor has spread to other parts of the body) sites.
All Cause Mortality
	Chemohormonal and Definitive Therapy
	Affected / at Risk (%)	# Events
Total	0/26 (0%)
Serious Adverse Events
	Chemohormonal and Definitive Therapy
	Affected / at Risk (%)	# Events
Total	2/26 (7.7%)
Blood and lymphatic system disorders
neutropenic fever	1/26 (3.8%)	1
Gastrointestinal disorders
abdominal pain	1/26 (3.8%)	1
partial bowel obstruction	1/26 (3.8%)	1
Injury, poisoning and procedural complications
back pain	1/26 (3.8%)	1
Other (Not Including Serious) Adverse Events
	Chemohormonal and Definitive Therapy
	Affected / at Risk (%)	# Events
Total	26/26 (100%)
Blood and lymphatic system disorders
anemia	1/26 (3.8%)	1
white blood cell decreased	3/26 (11.5%)	4
neutrophil count decreased	1/26 (3.8%)	2
lymphocyte count decreased	1/26 (3.8%)	1
Ear and labyrinth disorders
tinnitus	1/26 (3.8%)	1
Eye disorders
blurred vision	1/26 (3.8%)	1
floater eyes	1/26 (3.8%)	1
Gastrointestinal disorders
constipation	2/26 (7.7%)	2
abdominal pain	2/26 (7.7%)	2
diarrhea	2/26 (7.7%)	2
nausea	4/26 (15.4%)	5
xerostomia	2/26 (7.7%)	3
(GERD)gastroesophageal reflux disease	1/26 (3.8%)	1
General disorders
edema	5/26 (19.2%)	6
fatigue	15/26 (57.7%)	15
infusion reaction	1/26 (3.8%)	2
Hepatobiliary disorders
bilirubin increased	1/26 (3.8%)	1
Infections and infestations
pruritus	1/26 (3.8%)	1
Investigations
alkaline phosphatase increased	1/26 (3.8%)	1
weight gain	1/26 (3.8%)	1
(Serum Glutamic-Oxaloacetic Transaminase)SGOT increased	1/26 (3.8%)	2
(Serum Glutamic-Pyruvic Transaminase) SGPT increased	1/26 (3.8%)	1
Metabolism and nutrition disorders
hyperglycemia	3/26 (11.5%)	4
Musculoskeletal and connective tissue disorders
bone pain	2/26 (7.7%)	2
back pain	2/26 (7.7%)	2
muscle aches	1/26 (3.8%)	1
Nervous system disorders
nerve pain	1/26 (3.8%)	1
headache	2/26 (7.7%)	2
dysgeusia	2/26 (7.7%)	2
neuropathy	6/26 (23.1%)	7
intermittent dizziness	1/26 (3.8%)	1
metallic taste	1/26 (3.8%)	1
Psychiatric disorders
insomnia	3/26 (11.5%)	3
decreased libido	1/26 (3.8%)	1
stress incontinence	2/26 (7.7%)	2
Renal and urinary disorders
urinary incontinence	3/26 (11.5%)	4
hematuria	2/26 (7.7%)	2
Respiratory, thoracic and mediastinal disorders
cough	3/26 (11.5%)	3
hoarseness	2/26 (7.7%)	2
hiccups	3/26 (11.5%)	3
Skin and subcutaneous tissue disorders
alopecia	3/26 (11.5%)	3
flushed face	1/26 (3.8%)	1
right arm rash	1/26 (3.8%)	1
Vascular disorders
hot flashes	11/26 (42.3%)	11
hypertension	1/26 (3.8%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.