This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.
Recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Abiraterone | CB 7598 | Arm I (SST) |
| Bicalutamide | Casodex, Cosudex, ICI 176,334, ICI 176334 | Arm I (SST) |
| Degarelix | FE200486, Firmagon | Arm I (SST) |
| Docetaxel | Docecad, RP56976, Taxotere, Taxotere Injection Concentrate | Step 1 (pre-randomization) |
| Flutamide | 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 | Arm I (SST) |
| Goserelin Acetate | ZDX, Zoladex | Arm I (SST) |
| Histrelin Acetate | Supprelin, Vantas | Arm I (SST) |
| Leuprolide Acetate | 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 | Arm I (SST) |
| Nilutamide | Anandron, Nilandron, RU-23908 | Arm I (SST) |
| Prednisone | .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 | Step 1 (pre-randomization) |
| Triptorelin | 6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, CL-118,532, Decapeptyl, Detryptoreline | Arm I (SST) |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Arm I (SST) | Active Comparator | Participants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone. |
|
| Arm II (SST, prostatectomy or radiation therapy) | Experimental | 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. |
|
| Step 1 (pre-randomization) | Active Comparator | Standard treatment data collection prior to randomization |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
| Measure: | Overall survival (OS) |
| Time Frame: | From date of randomization to date of death due to any cause, assessed up to 8 years |
| Safety Issue: | |
| Description: |
| Measure: | Media OS |
| Time Frame: | From date of randomization to date of death due to any cause, assessed up to 8 years |
| Safety Issue: | |
| Description: | Will compare OS in metastatic prostate cancer patients who received standard systemic therapy (SST) plus surgical excision of the primary tumor versus SST alone in the subset who specify the surgical intent stratification factor. |
| Measure: | Rate of symptomatic local progression |
| Time Frame: | Up to 8 years |
| Safety Issue: | |
| Description: | Defined as any of the following events post-randomization: Common Terminology Criteria for Adverse Events version 5 grade >= 2 hematuria, urinary retention, urinary tract obstruction, urinary tract pain, pelvic pain, renal and urinary disorders-other. Will be compared between the treatment arms. A proportional hazards model will be fit to each of these endpoints where the time interval starts at date of randomization to (i) time of first symptomatic local progression or ii) progression or death due to any cause, where those without the event are censored at their last contact date. Stratification factors will be adjusted for as covariates. |
| Measure: | Progression-free survival (PFS) |
| Time Frame: | From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 8 years |
| Safety Issue: | |
| Description: | Will be compared between for the subsets of patients with and without metastasis directed therapy (MDT) to oligometastatic sites. A proportional hazards model will be fit to each of these endpoints where the time interval starts at date of randomization to (i) time of first symptomatic local progression or ii) progression or death due to any cause, where those without the event are censored at their last contact date. Stratification factors will be adjusted for as covariates. |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Southwest Oncology Group |
June 3, 2021
