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

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ClinicalTrials.gov Identifier: NCT03070886
Recruitment Status : Recruiting
First Posted : March 6, 2017
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Tracking Information
First Submitted Date  ICMJE December 30, 2016
First Posted Date  ICMJE March 6, 2017
Last Update Posted Date January 29, 2019
Actual Study Start Date  ICMJE January 16, 2017
Estimated Primary Completion Date May 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Freedom from progression (FFP) (Phase II) [ Time Frame: From time of randomization to first event, assessed up to 43 months ]
    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.
  • Metastasis free survival (MFS) (Phase III) [ Time Frame: From time of randomization to first occurrence of distant metastasis or death from any cause, assessed up to 9.5 years ]
    Will be measured with a one-sided stratified log-rank test when 282 MFS events have been observed. Both unadjusted and adjusted hazard ratios and the respective 95% confidence interval will be computed.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03070886 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Overall survival [ Time Frame: Time to death from any cause assessed up to 9.5 years ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • Proportion of undetectable PSA with a non-castrate testosterone [ Time Frame: At 2.5 years post treatment ]
    Both unadjusted and adjusted odds ratios and the respective 95% confidence interval will be computed.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Antiandrogen Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With Prostate Cancer That Has Been Removed by Surgery
Official Title  ICMJE Phase II-III Trial of Adjuvant Radiotherapy Following Radical Prostatectomy With or Without Adjuvant Docetaxel
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Stage I Prostate Adenocarcinoma
  • Stage II Prostate Adenocarcinoma
  • Stage III Prostate Adenocarcinoma
Intervention  ICMJE
  • Drug: Bicalutamide
    Given orally
    Other Names:
    • Casodex
    • Cosudex
    • ICI 176,334
    • ICI 176334
  • Drug: Docetaxel
    Given IV
    Other Names:
    • Docecad
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Radiation: External Beam Radiation Therapy
    Undergo external beam radiation therapy
    Other Names:
    • Definitive Radiation Therapy
    • EBRT
    • External Beam Radiotherapy
    • External Beam RT
    • external radiation
    • External Radiation Therapy
    • external-beam radiation
  • Drug: Flutamide
    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
    Other Names:
    • ZDX
    • Zoladex
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Leuprolide Acetate
    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
    Other Names:
    • Anandron
    • Nilandron
    • RU-23908
Study Arms  ICMJE
  • Active Comparator: Arm I (androgen deprivation therapy, EBRT)
    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 EBRT for 7.5 weeks.
    Interventions:
    • Drug: Bicalutamide
    • Radiation: External Beam Radiation Therapy
    • Drug: Flutamide
    • Drug: Goserelin Acetate
    • Other: Laboratory Biomarker Analysis
    • Drug: Leuprolide Acetate
    • Drug: Nilutamide
  • Experimental: Arm II (androgen deprivation therapy, EBRT, docetaxel)
    Patients 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.
    Interventions:
    • Drug: Bicalutamide
    • Drug: Docetaxel
    • Radiation: External Beam Radiation Therapy
    • Drug: Flutamide
    • Drug: Goserelin Acetate
    • Other: Laboratory Biomarker Analysis
    • Drug: Leuprolide Acetate
    • Drug: Nilutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2017)
612
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2031
Estimated Primary Completion Date May 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mark Hurwitz, MD 215-955-5485 mark.hurwitz@jeffersonhospital.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03070886
Other Study ID Numbers  ICMJE NRG-GU002
NCI-2016-00963 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GU002
NRG-GU002 ( Other Identifier: NRG Oncology )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NRG Oncology
Study Sponsor  ICMJE NRG Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Mark Hurwitz, MD NRG Oncology
PRS Account NRG Oncology
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP