Clinical Trials /

Antiandrogen Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With Prostate Cancer That Has Been Removed by Surgery

NCT03070886

Description:

This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Antiandrogen Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With Prostate Cancer That Has Been Removed by Surgery
  • Official Title: Phase II-III Trial of Adjuvant Radiotherapy Following Radical Prostatectomy With or Without Adjuvant Docetaxel

Clinical Trial IDs

  • ORG STUDY ID: NRG-GU002
  • SECONDARY ID: NCI-2016-00963
  • SECONDARY ID: NRG-GU002
  • SECONDARY ID: NRG-GU002
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03070886

Conditions

  • Stage I Prostate Adenocarcinoma
  • Stage II Prostate Adenocarcinoma
  • Stage III Prostate Adenocarcinoma

Interventions

DrugSynonymsArms
BicalutamideCasodex, Cosudex, ICI 176,334, ICI 176334Arm I (androgen deprivation therapy, EBRT)
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateArm II (androgen deprivation therapy, EBRT, docetaxel)
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 (androgen deprivation therapy, EBRT)
Goserelin AcetateZDX, ZoladexArm I (androgen deprivation therapy, EBRT)
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 (androgen deprivation therapy, EBRT)
NilutamideAnandron, Nilandron, RU-23908Arm I (androgen deprivation therapy, EBRT)

Purpose

This randomized phase II/III trial studies docetaxel, antiandrogen therapy, and radiation therapy to see how well it works compared with antiandrogen therapy and radiation therapy alone in treating patients with prostate cancer that has been removed by surgery. Androgen can cause the growth of prostate cells. Antihormone therapy may lessen the amount of androgen made by the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving antiandrogen therapy and radiation therapy with or without docetaxel after surgery may kill any remaining tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the benefit of docetaxel as measured by improvement in freedom from progression
      (phase II) and subsequently metastasis free survival (phase III) when given in combination
      with radiation and androgen deprivation in treatment of high risk prostate cancer
      post-radical prostatectomy.

      SECONDARY OBJECTIVES:

      I. To assess overall survival. II. To assess local time to progression. III. To assess
      undetectable prostate-specific antigen (PSA) with a non-castrate testosterone at 2.5 years
      post treatment.

      IV. To assess the utility of genomic profiling in making adjuvant therapy decisions
      post-prostatectomy.

      V. To assess toxicity of docetaxel in the post-operative setting when combined with
      radiation and androgen deprivation therapy.

      VI. To assess treatment response by genomically defined sub-groups of prostate cancer
      patients.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive androgen deprivation therapy comprising leuprolide acetate,
      goserelin acetate, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks
      after the start of androgen deprivation therapy, patients receive external beam radiation
      therapy (EBRT) for 7.5 weeks.

      ARM II: Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks
      after completion of radiation therapy, patients receive docetaxel intravenously (IV) on day
      1 of every 21 days for 6 courses in the absence of disease progression or unexpected
      toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      then every 6 months for 3 years, and then yearly.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (androgen deprivation therapy, EBRT)Active ComparatorPatients receive androgen deprivation therapy comprising leuprolide acetate, goserelin acetate, bicalutamide, flutamide, or nilutamide for 6 months. Beginning 8 weeks after the start of androgen deprivation therapy, patients receive EBRT for 7.5 weeks.
  • Bicalutamide
  • Flutamide
  • Goserelin Acetate
  • Leuprolide Acetate
  • Nilutamide
Arm II (androgen deprivation therapy, EBRT, docetaxel)ExperimentalPatients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV on day 1 of every 21 days for 6 courses in the absence of disease progression or unexpected toxicity.
  • Bicalutamide
  • Docetaxel
  • Flutamide
  • Goserelin Acetate
  • Leuprolide Acetate
  • Nilutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Patients post-prostatectomy with baseline Gleason >= 7 (per prostatectomy pathology)
             and baseline PSA nadir >= 0.2 ng/ml obtained prior to step 1 registration

          -  Baseline testosterone level obtained post prostatectomy prior to step 1 registration

          -  Pathologically (histologically) proven diagnosis of adenocarcinoma of the prostate as
             confirmed at time of prostatectomy; prostatectomy must have been performed =< 365
             days (1 year) prior to step 1 registration

          -  Primary treatment with radical prostatectomy

          -  Any type of radical prostatectomy is permitted, including retropubic, perineal,
             laparoscopic or robotically assisted

          -  Prior ablative treatment for treatment of benign prostatic hypertrophy or focal
             high-intensity focused ultrasound therapy (HIFU) prior to prostatectomy is allowed

          -  Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist
             and/or non-steroidal anti-androgen) is allowed if discontinued at least 90 days prior
             to study enrollment and given for =< 90 days duration; finasteride or dutasteride
             must be stopped before treatment but should not determine eligibility; for patients
             on prior LHRH analogs, the discontinuation date should be calculated based the
             expected duration of the sustained release injection, not simply the injection date
             of the drug

          -  Pathologically proven to be lymph node negative by pelvic lymphadenectomy (pN0) or
             lymph node status pathologically unknown (undissected pelvic lymph nodes [pNx])

          -  Any pT-stage based on American Joint Committee on Cancer 7th edition is acceptable
             for study entry based on the following diagnostic workup:

               -  History/physical examination within 60 days prior to step 1 registration

               -  No distant metastases, based upon the following minimum diagnostic workup:

               -  A computed tomography (CT) scan of the abdomen and pelvis (with contrast if
                  renal function is acceptable; a CT without contrast is permitted if the patient
                  is not a candidate for contrast) or magnetic resonance imaging (MRI) of the
                  pelvis within 120 days prior to step 1 registration; lymph nodes will be
                  non-metastatic unless they measure more than 1.5 cm short axis;

               -  Bone scan within 120 days prior to step 1 registration (a sodium fluoride [NaF]
                  positron emission tomography/computed tomography [PET/CT] is an acceptable
                  substitute); if the bone scan is suspicious, a plain x-ray, CT scan, NaF PET/CT
                  and/or MRI must be obtained to rule out metastasis

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 1 within 90 days
             prior to step 1 registration

          -  Platelets >= 1 X 10^6 cells/mm^3 (100,000) based upon complete blood count (CBC)

          -  Hemoglobin >= 10.0 g/dl based upon CBC (Note: The use of transfusion or other
             intervention to achieve Hgb >= 10.0 g/dl is not allowed)

          -  Absolute neutrophil count greater than 1.5 x 10^9/L (1500)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5 x the upper
             limit of normal

          -  Total bilirubin normal unless history of Gilbert's syndrome

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to step 1 registration

          -  Available surgical formalin-fixed paraffin-embedded (FFPE) specimen for genomic
             analysis on DECIPHER Genomic Resource Information Database (GRID) platform

        Exclusion Criteria:

          -  Definitive clinical or radiologic evidence of metastatic disease

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 2 years) Ta bladder cancer is not considered invasive

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
             different cancer is allowable if completed more than two years prior to step 1
             registration; prior androgen deprivation is allowed

          -  Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused
             ultrasound [HIFU]) for prostate cancer is allowed; prior focal HIFU or treatment for
             benign prostatic hypertrophy is allowed

          -  Prostatectomy performed greater than 365 days (1 year) prior to step 1 registration

          -  Severe and/or active co-morbidity defined as follows:

               -  History of inflammatory bowel disease

               -  History of active hepatitis B or C; blood tests are not required to determine if
                  the patient has had hepatitis B or C, unless the patient reports a history of
                  hepatitis

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               -  Transmural myocardial infarction within the last 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the
                  time of step 1 registration

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization within 15 days of step 1 registration or precluding
                  study therapy at the time of step 1 registration

               -  Uncontrolled severe illness or medical condition (including uncontrolled
                  diabetes), which in the judgment of the treating physician would make the
                  administration of chemotherapy inadvisable

               -  Concurrent or planned treatment with strong inhibitors (e.g. ketoconazole,
                  clarithromycin, etcetera [etc]) or strong inducers (e.g. carbamazepine,
                  phenytoin, rifampin, phenobarbital, efavirenz, tipranavir, St. John's wort) of
                  cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who
                  are already on these treatments)

          -  Human immunodeficiency virus (HIV) positive with cluster of differentiation 4 (CD4)
             count < 200 cells/microliter; note that patients who are HIV positive are eligible,
             provided they are under treatment with highly active antiretroviral therapy (HAART)
             and have a CD4 count >= 200 cells/microliter within 30 days prior to step 1
             registration; note also that HIV testing is not required for eligibility for this
             protocol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Freedom from progression (FFP) (Phase II)
Time Frame:From time of randomization to first event, assessed up to 43 months
Safety Issue:
Description:Will be determined with a one-sided stratified log-rank test when 89 FFP events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed. Events for FFP will be the first occurrence of biochemical failure by PSA >= 0.4 ng/ml over the nadir PSA confirmed by a second PSA higher than the first by any amount, recurrence (local, regional or distant), institution of secondary androgen deprivation therapy and death from any cause.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Time to death from any cause assessed up to 9.5 years
Safety Issue:
Description:Will be analyzed using log-rank methodology and Cox proportional models. Tests for violations of proportionality will performed for the survival models. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Measure:Time to local progression
Time Frame:Baseline to local or regional recurrence ignoring biochemical failure and distant recurrence and censoring for death, assessed up to 2.5 years
Safety Issue:
Description:Data will be summarized by cumulative incidence curves. Fine and Gray models will be used to adjust inference for competing risks. Both unadjusted and adjusted hazard ratios and the respective 95% confidence intervals will be computed.
Measure:Proportions of patients with Grade 3 through Grade 5 adverse events that are either related to study drug or not graded according to NCI CTCAE version 3.0
Time Frame:Up to 30 days post radiation therapy
Safety Issue:
Description:Frequencies, proportions and severity of acute adverse events by treatment arm will be presented. Specifically, Grade 3 - 5 adverse events will be tallied. Adverse events related to study drug will also be tallied.
Measure:Proportion of undetectable PSA with a non-castrate testosterone
Time Frame:At 2.5 years post treatment
Safety Issue:
Description:Both unadjusted and adjusted odds ratios and the respective 95% confidence interval will be computed.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NRG Oncology

Last Updated

February 28, 2017