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Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00936390
First received: July 8, 2009
Last updated: July 21, 2014
Last verified: July 2014

July 8, 2009
July 21, 2014
September 2009
December 2020   (final data collection date for primary outcome measure)
Overall survival (OS) [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]
Overall survival (OS) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00936390 on ClinicalTrials.gov Archive Site
  • Biochemical failure according to the Phoenix (nadir + 2) definition [ Time Frame: From the date of randomization to the date of first documented rise in PSA of 2 ng/ml above the post treatment nadir value. ] [ Designated as safety issue: No ]
  • Local recurrence [ Time Frame: From the date of randomization to the date of first palpable progression or pathologic confirmation of local progression or to the date of first biochemical failure (nadir +2ng/ml) once the possibility of distant metastasis is ruled out. ] [ Designated as safety issue: No ]
  • Regional recurrence [ Time Frame: From the date of randomization to the date of first documented progression in pelvic lymph nodes or the date of first documented biochemical failure (BCF) if the CT of the pelvis was prompted by a BCF. ] [ Designated as safety issue: No ]
  • Distant metastasis [ Time Frame: From the date of randomization to the date of first documented metastatic disease by any measure or to the date of first documented biochemical failure if diagnostic imaging is prompted by BCF. ] [ Designated as safety issue: No ]
  • Prostate cancer-specific mortality [ Time Frame: From the date of randomization to the date of death due to prostate cancer/complication of treatment. ] [ Designated as safety issue: No ]
  • Non-prostate cancer-specific mortality [ Time Frame: From the date of randomization to the date of death without the evidence of prostate cancer/complication of treatment. ] [ Designated as safety issue: No ]
  • Rate of salvage androgen-deprivation therapy [ Time Frame: From the end of treatment to the date of first administration of ADT. ] [ Designated as safety issue: No ]
  • Rates of OS for patients treated with the 3 different radiotherapy modalities in each arm [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]
  • Incidence of "acute" adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v. 4.0 [ Time Frame: From the start of radiation therapy (RT) to first occurrence of worse severity of adverse event within 30 days after the completion of RT. ] [ Designated as safety issue: Yes ]
  • Time to "late" grade 3+ adverse events as assessed by NCI CTCAE v. 4.0 [ Time Frame: From the date of completion of RT to the date of first grade 3 or above adverse event occurring 30 days after the completion of RT. ] [ Designated as safety issue: Yes ]
  • Freedom from Failure [ Time Frame: From date of randomization to the date of first event of biochemical failure or local recurrence or regional reccurrence or distant metastasis. ] [ Designated as safety issue: No ]
  • Comparison of prostate cancer-specific health related quality of life (HRQOL) change as measured by EPIC [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  • Comparison of fatigue status as measured by the Patient Reported Outcome Measurement Information System (PROMIS) fatigue domain [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  • Assessment and comparison of Quality Adjusted Life Years (QALYs) [ Time Frame: From date of randomization to the following times: last week of RT, 6 months, 1 year and 5 years post RT. ] [ Designated as safety issue: No ]
  • Correlation between the fatigue PROMIS score change and plasma cytokine change [ Time Frame: From date of randomization to 3 weeks from start of RT. ] [ Designated as safety issue: No ]
  • Biochemical failure according to the Phoenix (nadir + 2) definition [ Designated as safety issue: No ]
  • Local recurrence [ Designated as safety issue: No ]
  • Regional recurrence [ Designated as safety issue: No ]
  • Distant metastasis [ Designated as safety issue: No ]
  • Prostate cancer-specific mortality [ Designated as safety issue: No ]
  • Non-prostate cancer-specific mortality [ Designated as safety issue: No ]
  • Rate of salvage ADT [ Designated as safety issue: No ]
  • Rates of OS for patients treated with the 3 different RT modalities in each arm [ Designated as safety issue: No ]
  • Incidence of "acute" adverse events as assessed by NCI CTCAE v. 3.0 [ Designated as safety issue: Yes ]
  • Time to "late" grade 3+ adverse events as assessed by NCI CTCAE v. 3.0 [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer
A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients With Intermediate-Risk Prostate Cancer

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer.

OBJECTIVES:

Primary

  • Demonstrate an overall survival (OS) advantage in patients with intermediate-risk prostate cancer treated with dose-escalated radiotherapy (RT) with versus without short-term androgen-deprivation therapy (ADT).

Secondary

  • Determine whether the addition of ADT to dose-escalated RT versus RT alone improves clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of salvage ADT, and prostate cancer-specific mortality in these patients.
  • Estimate the magnitude of benefit of ADT with respect to OS in patients treated with different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate brachytherapy boost vs high-dose rate brachytherapy boost).
  • Compare acute and late treatment adverse events of these regimens and correlate these events with the presence or absence of pre-existing comorbidity as documented by the Adult Comorbidity Evaluation 27 assessment.

OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs < 2), and radiotherapy (RT) modality (dose-escalated external-beam RT [EBRT] vs EBRT and low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo EBRT* once daily on days 1-5 for about 9 weeks (44 treatments). Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy implant on days 1-5 for about 5 weeks (25 treatments). NOTE: *Type of RT is at discretion of treating physician and may include either 3D-conformal RT or intensity-modulated RT.
  • Arm II: Patients receive androgen-deprivation therapy comprising luteinizing-hormone releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin) subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy (flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks after the first LHRH injection, patients undergo radiotherapy as in arm I.

After completion of study therapy, patients are followed up periodically.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: bicalutamide
    Given orally
  • Drug: buserelin
    Given subcutaneously or as an injection
  • Drug: flutamide
    Given orally
  • Drug: goserelin acetate
    Given subcutaneously or as an injection
  • Drug: leuprolide acetate
    Given subcutaneously or as an injection
  • Drug: triptorelin
    Given subcutaneously or as an injection
  • Radiation: 3-dimensional conformal radiation therapy
    Given as external-beam radiation therapy
  • Radiation: intensity-modulated radiation therapy
    Given as external-beam radiation therapy
  • Active Comparator: Arm I
    Patients undergo external-beam radiation therapy (EBRT) once daily on days 1-5. Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy implant.
    Interventions:
    • Radiation: 3-dimensional conformal radiation therapy
    • Radiation: intensity-modulated radiation therapy
  • Experimental: Arm II
    Patients receive androgen-deprivation therapy comprising luteinizing-hormone releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin) subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy (flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks after the first LHRH injection, patients undergo radiotherapy as in arm I.
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: flutamide
    • Drug: goserelin acetate
    • Drug: leuprolide acetate
    • Drug: triptorelin
    • Radiation: 3-dimensional conformal radiation therapy
    • Radiation: intensity-modulated radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1520
Not Provided
December 2020   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate diagnosed within the past 180 days and at intermediate-risk for recurrence by meeting ≥ 1 of the following criteria:

    • Gleason score > 7
    • Prostate Specific Antigen (PSA) > 10 and ≤ 20 ng/mL

      • Baseline serum PSA value performed within 60 days with an FDA-approved assay (e.g., Abbott, Hybritech)
      • Baseline PSA must not be obtained during any of the following time frames:10-day period after prostate biopsy, after initiation of androgen-deprivation therapy, or within the past 30 days after discontinuation of finasteride (90 days for dutasteride)
    • Clinical stage T2b or T2c disease
    • Patients previously diagnosed with low-risk (Gleason score < 6, clinical stage < T2a, and PSA < 10 ng/mL) prostate cancer undergoing active surveillance who are re-biopsied and found to have intermediate-risk disease according to the protocol criteria are eligible for enrollment within 6 months of the repeat biopsy procedure
  • Patients with Gleason Score ≥ 8, PSA > 20 ng/mL, OR clinical stage ≥ T3 are ineligible for this trial

    • If findings of extracapsular extension or seminal vesicle invasion are noted on prostate MRI, this study, if used, will not render patients ineligible for accrual to this protocol
    • Primary tumor staging for eligibility purposes is to be based on palpable or core biopsy evidence only with respect to extracapsular extension or seminal vesicle involvement
  • No patients with all 3 intermediate-risk factors who also have ≥ 50% of the number of their biopsy cores positive for cancer

    • The percentage of biopsy cores involved will only be considered with respect to eligibility for those patients with all 3 of the above risk factors (i.e., patients with one or two of the above risk factors are eligible irrespective of the percentage of biopsy cores involved)
  • Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT scan or MRI), nodal sampling, or dissection within the past 60 days (required for patients with 2-3 risk factors)

    • Abdominal imaging not required for a single intermediate-risk factor (these studies may be obtained at the discretion of the treating physician)
    • Lymph nodes that are equivocal or questionable by imaging allowed without biopsy if nodes ≤ 1.5 cm
    • Any node > 1.5 cm on imaging requires a negative biopsy
  • No evidence of bone metastases on bone scan within the past 60 days

    • Bone scan not required for patients with a single intermediate-risk factor (scan may be obtained at the discretion of the treating physician)
    • Equivocal bone scan findings allowed if plain film x-rays negative for metastasis

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute neutrophil count (ANC) ≥ 1,800/mm^3*
  • Platelet count ≥ 100,000/mm^3*
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve level allowed)*
  • NOTE: *For patients undergoing brachytherapy only.
  • Fertile patients must use effective contraception during and for the 3 months after cessation of protocol treatment
  • No invasive malignancy or hematological malignancy (e.g., leukemia, lymphoma, myeloma) within the past 5 years except adequately treated non-melanomatous skin cancer

    • Prior diagnoses of carcinoma in situ allowed
  • No severe or active co-morbidity with any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy, within the past 30 days
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

      • Laboratory tests for liver function and coagulation parameters not required for entry into this protocol
    • AIDS based upon current Centers for Disease Control (CDC) definition

      • HIV testing not required for entry into this protocol
      • HIV-seropositive patients who do not meet criteria for diagnosis of AIDS allowed

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radical surgery (prostatectomy), high-intensity focused ultrasound, or cryosurgery for prostate cancer
  • No prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral orchiectomy
  • No finasteride within past 30 days (90 days for dutasteride)
  • No prior or concurrent cytotoxic chemotherapy for prostate cancer

    • Prior chemotherapy for a different cancer allowed
  • No prior radiotherapy (RT), including brachytherapy, to the region of the study cancer that would result in overlap of RT fields

    • Patients undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume < 60 cc, American Urological Association (AUA) score ≤ 15 within the past 60 days of registration, and no history of prior transurethral resection of the prostate (TURP)
    • TURP allowed for patients who receive external-beam radiation therapy only
Male
18 Years and older
No
United States,   Canada
 
NCT00936390
RTOG 0815, CDR0000648194, NCI-2011-01948
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • NRG Oncology
Study Chair: Alvaro A. Martinez, MD, FACR 21st Century Oncology - Michigan Institute for Radiation Oncology
Radiation Therapy Oncology Group
July 2014

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