Clinical Trials /

Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer

NCT03678025

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
  • Official Title: Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: S1802
  • SECONDARY ID: NCI-2018-01738
  • SECONDARY ID: S1802
  • SECONDARY ID: S1802
  • SECONDARY ID: U10CA180888
  • NCT ID: NCT03678025

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

Interventions

DrugSynonymsArms
AbirateroneCB 7598Arm I (SST)
BicalutamideCasodex, Cosudex, ICI 176,334, ICI 176334Arm I (SST)
DegarelixFE200486, FirmagonArm I (SST)
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateStep 1 (pre-randomization)
Flutamide4'-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, TestotardArm I (SST)
Goserelin AcetateZDX, ZoladexArm I (SST)
Histrelin AcetateSupprelin, VantasArm I (SST)
Leuprolide AcetateA-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, ViadurArm I (SST)
NilutamideAnandron, Nilandron, RU-23908Arm 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-PrednisoneStep 1 (pre-randomization)
Triptorelin6-D-Tryptophan-LH-RH, 6-D-Tryptophanluteinizing Hormone-releasing Factor, AY-25650, CL-118,532, Decapeptyl, DetryptorelineArm I (SST)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (SST)Active ComparatorParticipants receive 1 acceptable form of SST as in Induction except for treatment with docetaxel and prednisone.
  • Abiraterone
  • Bicalutamide
  • Degarelix
  • Flutamide
  • Goserelin Acetate
  • Histrelin Acetate
  • Leuprolide Acetate
  • Nilutamide
  • Triptorelin
Arm II (SST, prostatectomy or radiation therapy)ExperimentalParticipants 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.
  • Abiraterone
  • Bicalutamide
  • Degarelix
  • Flutamide
  • Goserelin Acetate
  • Histrelin Acetate
  • Leuprolide Acetate
  • Nilutamide
  • Triptorelin
Step 1 (pre-randomization)Active ComparatorStandard treatment data collection prior to randomization
  • Abiraterone
  • Bicalutamide
  • Degarelix
  • Docetaxel
  • Flutamide
  • Goserelin Acetate
  • Histrelin Acetate
  • Leuprolide Acetate
  • Nilutamide
  • Prednisone
  • Triptorelin

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

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:

Secondary Outcome Measures

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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Southwest Oncology Group

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