The MetroHealth System

Conditions

Castration Levels of Testosterone
Metastatic Prostatic Adenocarcinoma
Stage IV Prostate Cancer AJCC v8
Stage IVA Prostate Cancer AJCC v8
Stage IVB Prostate Cancer AJCC v8

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: Male
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

- STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a
histologically or cytologically proven diagnosis of adenocarcinoma of the prostate.
Patients with pure small cell carcinoma* (SCC), sarcomatoid, or squamous cell
carcinoma are not eligible. (*morphology must be consistent with SCC; synaptophysin
or chromogranin positive by immunohistochemical staining is insufficient to diagnose
SCC).

- STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact
prostate. No prior local therapy for prostate adenocarcinoma is allowed (e.g.,
brachytherapy, high-intensity focused ultrasound [HIFU], cryotherapy, laser ablative
therapies). Any prior therapy for benign conditions, such as obstruction, are
acceptable (e.g., transurethral resection of the prostate, greenlight laser
ablation, microwave ablation).

- STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of
metastatic disease on technetium bone scan and computed tomography (CT) or magnetic
resonance imaging (MRI) within 42 days prior to starting standard systemic therapy.
Metastatic disease that is detected by positron emission tomography (PET) scan only
(sodium fluoride [NaF], prostate-specific membrane antigen [PSMA],
anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid [FACBC], carbon [C]11) but
not conventional imaging (technetium [Tc]99 bone scan, CT or MRI) or solitary
metastases by conventional imaging, must be confirmed histologically or
cytologically.

- STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases
are not eligible. Brain imaging studies are not required for eligibility if the
patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain
imaging studies are performed, they must be negative for disease.

- STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received
no more than 28 weeks of standard systemic therapy (SST). SST is defined as current
National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate
cancer.

- STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have
progressed while on SST.

- STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with
oligometastatic prostate cancer may receive metastasis directed therapy to up to
four sites of disease prior to randomization.

- STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete
physical examination and medical history within 28 days prior to registration.

- STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA
documented prior to initiation of SST and within 28 days prior to registration. Any
additional PSAs measured while receiving SST should be recorded.

- STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone
lab documented within 28 days prior to randomization. Any additional testosterone
labs measured while receiving SST should be recorded as well as pretreatment
initiation if available.

- STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is
allowed except for the following: adequately treated basal cell or squamous cell
skin cancer, adequately treated stage 0, I or II cancer from which the patient is
currently in complete remission, or any other cancer from which the patient has been
disease free for three years.

- STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the
opportunity to participate in translational medicine studies and specimen banking
for future studies.

- STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete
Patient-Reported Outcome instruments in English, Spanish or French, must participate
in the quality of life studies.

- STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines.

- STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: As a part of the OPEN registration
process the treating institution's identity is provided in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered in the system.

- STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of
disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or
MRI or symptomatic deterioration (as defined by physician discretion) within 28 days
prior to randomization.

- STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with
a urologist and have surgically resectable disease regardless of definitive
treatment intent or randomization.

- STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received
between 22 and 28 weeks of SST as measured from the date of first hormonal therapy
or surgical castration. SST is defined by current NCCN guidelines for metastatic
prostate cancer.

- STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be
planning to receive docetaxel after randomization.

- STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST
must have resolved to =< grade 1 (Common Terminology Criteria for Adverse Events
[CTCAE] version 5.0) prior to randomization.

- STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received
elective metastasis directed therapy to oligometastatic sites (=< 4 sites). All
treatment must be completed prior to randomization.

- STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA
performed within 28 days prior to randomization.

- STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a
testosterone < 50 ng/dL within 28 days prior to randomization.

- STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod
performance status of 0 ? 1 within 28 days prior to randomization.

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator Arm I (SST)	Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone.	Drug: Abiraterone Given PO Other names: CB 7598 Drug: Bicalutamide Given PO Other names: Casodex Cosudex ICI 176,334 ICI 176334 Drug: Degarelix Given via injection Other names: FE200486 Firmagon Drug: Flutamide Given PO Other names: 4'-Nitro-3'-trifluoromethylisobutyranilide Apimid Cebatrol Chimax Cytomid Drogenil Euflex Eulexine Flucinom Flucinome Flugerel Fluken Flulem FLUT Fluta-Gry Flutabene Flutacan Flutamex Flutamin Flutan Flutaplex Fugerel Grisetin Niftolide Oncosal Profamid Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)- Prostacur Prostadirex Prostica Prostogenat SCH 13521 Tafenil Tecnoflut Testotard Drug: Goserelin Acetate Given SC Other names: ZDX Zoladex Drug: Histrelin Acetate Receive SC Other names: Supprelin Vantas Drug: Leuprolide Acetate Receive SC or IM Other names: A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur Drug: Nilutamide Given PO Other names: Anandron Nilandron RU-23908 Procedure: Orchiectomy Undergo bilateral orchiectomy Other names: Castration Male Castration Male Gonadectomy orchidectomy Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Triptorelin injection Other names: 6-D-Tryptophan-LH-RH 6-D-Tryptophanluteinizing Hormone-releasing Factor AY-25650 CL-118,532 Decapeptyl Detryptoreline
Experimental Arm II (SST, prostatectomy or radiation therapy)	Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone. Participants undergo prostatectomy within 8 weeks after randomization or radiation therapy within 4 weeks of randomization.	Drug: Abiraterone Given PO Other names: CB 7598 Drug: Bicalutamide Given PO Other names: Casodex Cosudex ICI 176,334 ICI 176334 Drug: Degarelix Given via injection Other names: FE200486 Firmagon Drug: Flutamide Given PO Other names: 4'-Nitro-3'-trifluoromethylisobutyranilide Apimid Cebatrol Chimax Cytomid Drogenil Euflex Eulexine Flucinom Flucinome Flugerel Fluken Flulem FLUT Fluta-Gry Flutabene Flutacan Flutamex Flutamin Flutan Flutaplex Fugerel Grisetin Niftolide Oncosal Profamid Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)- Prostacur Prostadirex Prostica Prostogenat SCH 13521 Tafenil Tecnoflut Testotard Drug: Goserelin Acetate Given SC Other names: ZDX Zoladex Drug: Histrelin Acetate Receive SC Other names: Supprelin Vantas Drug: Leuprolide Acetate Receive SC or IM Other names: A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur Drug: Nilutamide Given PO Other names: Anandron Nilandron RU-23908 Procedure: Orchiectomy Undergo bilateral orchiectomy Other names: Castration Male Castration Male Gonadectomy orchidectomy Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Radiation: Radiation Therapy Standard radiation Other names: Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation Procedure: Radical Prostatectomy Standard surgery Other names: Prostatovesiculectomy Drug: Triptorelin injection Other names: 6-D-Tryptophan-LH-RH 6-D-Tryptophanluteinizing Hormone-releasing Factor AY-25650 CL-118,532 Decapeptyl Detryptoreline
Active Comparator Step 1 (pre-randomization)	Standard treatment data collection prior to randomization	Drug: Abiraterone Given PO Other names: CB 7598 Drug: Bicalutamide Given PO Other names: Casodex Cosudex ICI 176,334 ICI 176334 Drug: Degarelix Given via injection Other names: FE200486 Firmagon Drug: Docetaxel intravenous Other names: Docecad RP56976 Taxotere Taxotere Injection Concentrate Drug: Flutamide Given PO Other names: 4'-Nitro-3'-trifluoromethylisobutyranilide Apimid Cebatrol Chimax Cytomid Drogenil Euflex Eulexine Flucinom Flucinome Flugerel Fluken Flulem FLUT Fluta-Gry Flutabene Flutacan Flutamex Flutamin Flutan Flutaplex Fugerel Grisetin Niftolide Oncosal Profamid Propanamide, 2-Methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)- Prostacur Prostadirex Prostica Prostogenat SCH 13521 Tafenil Tecnoflut Testotard Drug: Goserelin Acetate Given SC Other names: ZDX Zoladex Drug: Histrelin Acetate Receive SC Other names: Supprelin Vantas Drug: Leuprolide Acetate Receive SC or IM Other names: A-43818 Abbott 43818 Abbott-43818 Carcinil Depo-Eligard Eligard Enanton Enantone Enantone-Gyn Ginecrin LEUP Leuplin Leuprorelin Acetate Lucrin Lucrin Depot Lupron Lupron Depot Lupron Depot-3 Month Lupron Depot-4 Month Lupron Depot-Ped Procren Procrin Prostap TAP-144 Trenantone Uno-Enantone Viadur Drug: Nilutamide Given PO Other names: Anandron Nilandron RU-23908 Procedure: Orchiectomy Undergo bilateral orchiectomy Other names: Castration Male Castration Male Gonadectomy orchidectomy Drug: Prednisone Given PO Other names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Other: Quality-of-Life Assessment Ancillary studies Other names: Quality of Life Assessment Drug: Triptorelin injection Other names: 6-D-Tryptophan-LH-RH 6-D-Tryptophanluteinizing Hormone-releasing Factor AY-25650 CL-118,532 Decapeptyl Detryptoreline

Recruiting Locations

MetroHealth Medical Center
Cleveland, Ohio 44109

Contact:
Site Public Contact
216-778-8526
dstrater@metrohealth.org

More Details

Status: Recruiting
Sponsor: SWOG Cancer Research Network

Study Contact

Dana Sparks, MAT
2106148808
dsparks@swog.org

Detailed Description

PRIMARY OBJECTIVES: I. To compare overall survival in metastatic prostate cancer patients who are randomized to standard systemic therapy (SST) plus definitive treatment of the primary tumor versus standard systemic therapy alone. SECONDARY OBJECTIVES: I. To compare overall survival in metastatic prostate cancer patients who received SST plus surgical excision of the primary tumor versus SST alone in the subset who specify the surgical intent stratification factor. II. To compare the rate of symptomatic local progression between the treatment arms. III. To compare progression-free survival (PFS) between the two treatment arms. IV. To compare rates of progression-free survival between arms for the subsets of patients with and without metastasis directed therapy (MDT) to oligometastatic sites. QUALITY OF LIFE OBJECTIVES: I. To compare between arms patient-reported urinary function and urinary bother over time (after initiation of SST at 6 months, 1, 2, and 3 years) using the Expanded Prostate Cancer Index Composite (EPIC) and patient-reported pain and physical functioning using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) between patients receiving standard systemic therapy and those receiving systemic therapy and definitive management of the primary prostate cancer. OTHER OBJECTIVES: I. To bank tissue and whole blood specimens for future use. OUTLINE: INDUCTION: Participants receive 1 of 6 acceptable forms of SST for 22-28 weeks. I. Participants undergo a bilateral orchiectomy. II. Participants receive goserelin acetate subcutaneously (SC) every 28 days or 12 weeks, histrelin acetate SC every 12 months, leuprolide acetate SC or intramuscularly (IM) every 1, 3, 4, or 6 months, and triptorelin every 1, 3, or 6 months. III. Participants receive goserelin acetate SC every 28 days or 12 weeks, histrelin acetate SC every 12 months, leuprolide acetate SC or IM every 1, 3, 4, or 6 months, and triptorelin every 1, 3, or 6 months. Participants also receive nilutamide orally (PO) daily, flutamide PO every 8 hours, and bicalutamide PO daily. IV. Participants receive degarelix via injection for 2 doses and then every 28 days. V. Participants receive nilutamide PO daily, flutamide PO every 8 hours, and bicalutamide PO daily. Participants also receive docetaxel over 1 hour every 3 weeks with or without prednisone PO every 12 hours. VI. Participants receive nilutamide PO daily, flutamide PO every 8 hours, and bicalutamide PO daily. Participants also receive abiraterone PO daily or prednisone PO every 12 hours. After completion of 22-28 weeks of SST, participants are then randomized to 1 of 2 arms. ARM I: Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone. ARM II: Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone. Participants undergo prostatectomy within 8 weeks after randomization or radiation therapy within 4 weeks of randomization. After completion of study treatment, participants are followed up for 8 years.