Radiation Therapy With or Without Bicalutamide for Recurr... | NCT00002874

Status Module

Name	Class
National Cancer Institute (NCI)	NIH
SWOG Cancer Research Network	NETWORK
NRG Oncology	OTHER

Description Module

Label	Type	Description	Intervention Names
Bicalutamide	Experimental	Radiation therapy + bicalutamide	Drug: bicalutamide Radiation: radiation therapy
Placebo	Placebo Comparator	Radiation therapy + placebo	Radiation: radiation therapy Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
bicalutamide	Drug	One (150 mg) tablet by mouth daily for two years beginning immediately upon, or just prior to, the initiation of irradiation.	Bicalutamide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (12-year Rates Reported)	Overall survival rates were estimated by the Kaplan-Meier method, with failure defined as death by any cause. Four-year follow-up was required of all patients, twelve-year rates are reported. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.	From date of randomization to 12 years.

Secondary Outcomes

Measure	Description	Time Frame
Non-Prostate Cancer Death (12-year Rates Reported)	Non-prostate cancer death rates were estimated by the cumulative incidence method, with failure defined as any death that does not fall into the following categories: death due to prostate cancer or complications of protocol treatment (centrally reviewed), death with known progressive metastatic disease while on salvage hormone therapy, or death with a known rising PSA while on salvage hormone therapy. All other deaths are considered competing risks. Patients alive at time of analysis were censored. Any other death was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Non-Prostate cancer death" is a more accurate wording for the protocol endpoint of "non-disease-specific survival", and matches the protocol definition.

Eligibility Module

Eligibility Criteria

Conditions for Patient Eligibility:

The patient on entry will have no clinical evidence of disease by physical exam or by imaging studies. A positive ProstaScint scan alone without a confirmatory biopsy must not be used to exclude a patient. Eligible patients will be those who have undergone a radical prostatectomy (either retropubic or perineal) and pelvic lymphadenectomy (either open or laparoscopic) for carcinoma of the prostate, pathologic stage T3N0, or pT2 pN0 with positive inked resection margin, at least 12 weeks prior to study entry.
Pathological T2 patients without positive margins, who are also pathologic N0 with prostatic fossa/anastamosis biopsy at the time of rising PSA documenting recurrent cancer, are eligible.
At entry, the PSA must be between 0.2 and 4.0ng/ml, inclusive.
A post-prostatectomy radioisotopic bone scan which was done within 16 weeks prior to entry must reveal no evidence of metastatic disease.
Patient must be evaluated by both the radiation oncologist and the urologist prior to entry and judged to be a suitable candidate for radiation and hormonal therapy.
Patient must have Karnofsky performance status >= 80.
Patients must have a life expectancy in excess of 10 years.
Patients must have, within 6 weeks prior to entry, a hemoglobin (Hgb) of >=10 gm, a white blood cell (WBC) count of >= 4000 cells/ml3, a platelet count of >= 100,000 cells/ml3, a serum bilirubin <= the institutional upper limit of normal, a serum serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) of <= 2.5 times the institutional upper limit of normal, and a serum creatinine of <= 2.0 times the institutional upper limit of normal.
A post-prostatectomy pelvic computerized tomography (CT) scan, within 16 weeks prior to randomization, must reveal no evidence of metastatic disease.
Patients must sign a study-specific informed consent form.
Patients with prior invasive cancers are eligible if disease free for at least 5 years; prior or concurrent basal or squamous cell skin cancer is eligible.

Conditions for Patient Ineligibility:

Pathologic stage T2 (without positive inked resection margin) or less except as stated in Section 3.1.1.1.
Pathologic lymph node stage of pN1 or greater.
An entry serum PSA of > 4.0ng/ml.
Patients with persistant urinary extravasation after prostatectomy.
Patients who have been previously treated with any hormonal therapy after prostatectomy.
Patients who have previously been treated with radiation therapy or biologic therapy for prostate cancer.
Karnofsky performance status < 80.
Treatment start > 4 weeks after randomization.
Prior chemotherapy for any reason.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
William U. Shipley, MD	Massachusetts General Hospital and Harvard Medical School, Boston	Principal Investigator
Himanshu R Lukka, MD	Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON	Study Chair
Pierre P Major, MD	Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON	Study Chair
Niall M Heney, MD	Massachusetts General Hospital and Harvard Medical School, Boston	Study Chair
David J Grignon, MD	Indiana University, Indianapolis	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham Comprehensive Cancer Center		Birmingham	Alabama	35294-3300	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28146658	Result	Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. doi: 10.1056/NEJMoa1607529.
36120850

ID	Type	URL	Comment
NCT00002874	Individual Participant Data Set	View IPD

Results Section

Participant Flow Module

ID	Title	Description
FG000	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
FG001	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Survival (12-year Rates Reported)

Overall survival rates were estimated by the Kaplan-Meier method, with failure defined as death by any cause. Four-year follow-up was required of all patients, twelve-year rates are reported. Four-year follow-up was required of all patients, but twelve-year rates were reported.

Patients are followed until death.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants	OG000394 OG001376

Title

Denominators

Categories

Title	Measurements
	OG00071.3(66.5 to 76.0) OG00176.3(71.9 to 80.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.020	One-sided significance level = 0.046 to preserve overall significance level of 0.05 for the study.	Hazard Ratio (HR)	0.77			2-Sided	95	0.59	0.98			Stratifying variables were fixed covariates: prior hormone therapy (yes/no), entry prostate-specific antigen (PSA) (1.6-4.0 vs. 0.2-1.5), PSA nadir after surgery (< 0.5 vs. >= 0.5), positive surgical margins (yes/no). Reference level = placebo arm.		Superiority

Secondary

Non-Prostate Cancer Death (12-year Rates Reported)

Non-prostate cancer death rates were estimated by the cumulative incidence method, with failure defined as any death that does not fall into the following categories: death due to prostate cancer or complications of protocol treatment (centrally reviewed), death with known progressive metastatic disease while on salvage hormone therapy, or death with a known rising PSA while on salvage hormone therapy. All other deaths are considered competing risks. Patients alive at time of analysis were censored. Any other death was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported.

Patients are followed until death. "Non-Prostate cancer death" is a more accurate wording for the protocol endpoint of "non-disease-specific survival", and matches the protocol definition.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Secondary

Second PSA Recurrence (12-year Rates Reported)

Second PSA recurrence (SPSAR) rates (i.e. first PSA failure on study) were estimated by the cumulative incidence method, with failure defined as the first occurrence of one of the following events: 1. Increase in PSA following protocol treatment according to the following criteria met during protocol treatment: If PSA dropped to undetectable level (<0.2 ng/ml) during protocol treatment (PT) then failure = increase after PT to >= 0.5 ng/ml ; If PSA decreased to a detectable level (≥ 0.2 ng/ml) during PT, then failure = increase PT of >= 0.3 ng/ml above the lowest detectable level; If PSA did not decrease during PT then failure = increase in PSA after PT of >= 0.5 ng/ml above entry PSA level. 2. The start of salvage hormone therapy. Patients alive without SPSAR at time of analysis were censored. Death without SPSAR was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Secondary

Third PSA Recurrence (12-year Rates Reported)

Third PSA recurrence rates (i.e. second PSA failure on study) were estimated by the cumulative incidence method, with failure defined as PSA value of 0.5ng/ml or higher or any disease progression after starting salvage hormone therapy. Patients alive without third PSA recurrence at time of analysis were censored. Death without third PSA recurrence was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Eligible patients who did not withdraw consent and who started salvage hormone therapy.

Posted

Number

95% Confidence Interval

percentage of participants

From start of salvage hormone therapy to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants

Secondary

PSA Complete Response at End of Protocol Treatment

Complete response is defined as a drop in PSA on protocol treatment to less than 0.2 ng/ml. Note that when the study opened many institutions could not detect PSA < 05 ng/ml.

Eligible patients who did not withdraw consent.

Posted

Count of Participants

Participants

End of protocol treatment, which is planned to last for two years

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants	OG000

Secondary

Distant Failure (12-year Rates Reported)

Distant failure rates were estimated by the cumulative incidence method, with failure defined as the first occurrence of distant failure. Patients alive without distant metastases at time of analysis were censored. Death without distant metastasis was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants	OG000

Secondary

Prostate Cancer Death (12-year Rates Reported)

Prostate cancer death rates were estimated by the cumulative incidence method, with failure defined as death due to prostate cancer or complications of protocol treatment (centrally reviewed), death with known progressive metastatic disease while on salvage hormone therapy, or death with a known rising PSA while on salvage hormone therapy. Patients alive at time of analysis were censored. Any other death was treated as a competing risk. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Prostate cancer death" is a more accurate wording for the protocol endpoint of "disease-specific survival", and matches the protocol definition.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants

Secondary

Progression-free Survival (12-year Rates Reported)

Progress-free survival rates were estimated by the Kaplan-Meier method, with failure defined as the first occurrence of PSA failure, local, regional or distant failure, or death from any cause. Patients alive without progression at time of analysis were censored. Four-year follow-up was required of all patients, but twelve-year rates were reported. Patients are followed until death. "Progression-free Survival" is more accurate wording for the protocol endpoint of "Freedom from Progression", and matches the protocol definition.

Eligible patients who did not withdraw consent.

Posted

Number

95% Confidence Interval

percentage of participants

From date of randomization to 12 years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts
Participants

Secondary

Grade 3+ Toxicity

Adverse events are graded using the Cooperative Group Common Toxicity Criteria and the Radiation Therapy Oncology Group (RTOG) Radiation Morbidity Scoring. Grade refers to severity, assigning Grades 1 through 5 based on this general guideline: Grade 0 None, Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related toxicity. Toxicities reported to have occurred within 90 days from the start of radiotherapy are reported as "Acute Radiotherapy", all later toxicities are reported as "Hormone therapy and late radiotherapy toxicity". The highest grade toxicity event per subject is counted within each of these time periods. Four-year follow-up was required of all patients; patients are followed until death.

Eligible patients who started protocol treatment and did not withdraw consent.

Posted

Number

participants

From date of randomization to four years.

ID	Title	Description
OG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
OG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute RT Toxicity: Hematologic: NOS	Blood and lymphatic system disorders	Coop. Group CTC	Systematic Assessment	EG0003 affected382 at risk EG0012 affected374 at risk
Hematologic: NOS	Blood and lymphatic system disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0005 affected382 at risk EG0015 affected374 at risk
Cardiac: NOS	Cardiac disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00018 affected382 at risk EG0016 affected374 at risk
Acute RT Toxicity: Bowel: NOS	Gastrointestinal disorders	Coop. Group CTC	Systematic Assessment	EG0001 affected382 at risk EG0013 affected374 at risk
Bowel/GI: NOS	Gastrointestinal disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00010 affected382 at risk EG0018 affected374 at risk
Nausea/vomiting: NOS	Gastrointestinal disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0001 affected382 at risk EG0011 affected374 at risk
Acute RT Toxicity: Other: NOS	General disorders	Coop. Group CTC	Systematic Assessment	EG0000 affected382 at risk EG0011 affected374 at risk
Other: NOS	General disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00016 affected382 at risk EG00116 affected374 at risk
Pain: NOS	General disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0002 affected382 at risk EG0016 affected374 at risk
Liver: NOS	Hepatobiliary disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0002 affected382 at risk EG0011 affected374 at risk
Neurologic: NOS	Nervous system disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0008 affected382 at risk EG0015 affected374 at risk
Acute RT Toxicity: Bladder: NOS	Renal and urinary disorders	Coop. Group CTC	Systematic Assessment	EG0004 affected382 at risk EG00111 affected374 at risk
Bladder/GU: NOS	Renal and urinary disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00028 affected382 at risk EG00130 affected374 at risk
Impotence: NOS	Reproductive system and breast disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00028 affected382 at risk EG00116 affected374 at risk
Dyspnea: NOS	Respiratory, thoracic and mediastinal disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0003 affected382 at risk EG0011 affected374 at risk
Skin-general: NOS	Skin and subcutaneous tissue disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG0002 affected382 at risk EG0013 affected374 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute RT Toxicity: Hematologic: NOS	Blood and lymphatic system disorders	Coop. Group CTC	Systematic Assessment	EG00034 affected382 at risk EG00128 affected374 at risk
Hematologic: NOS	Blood and lymphatic system disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00058 affected382 at risk EG00136 affected374 at risk
Cardiac: NOS	Cardiac disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00021 affected382 at risk EG00110 affected374 at risk
Acute RT Toxicity: Bowel: NOS	Gastrointestinal disorders	Coop. Group CTC	Systematic Assessment	EG000232 affected382 at risk EG001235 affected374 at risk
Bowel/GI: NOS	Gastrointestinal disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG000192 affected382 at risk EG001168 affected374 at risk
Nausea/vomiting: NOS	Gastrointestinal disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00019 affected382 at risk EG00112 affected374 at risk
Acute RT Toxicity: Other: NOS	General disorders	Coop. Group CTC	Systematic Assessment	EG00068 affected382 at risk EG00150 affected374 at risk
Other: NOS	General disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG000129 affected382 at risk EG001100 affected374 at risk
Pain: NOS	General disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00054 affected382 at risk EG00165 affected374 at risk
Acute RT Toxicity: Skin: NOS	Injury, poisoning and procedural complications	Coop. Group CTC	Systematic Assessment	EG00087 affected382 at risk EG00188 affected374 at risk
Skin-within XRT field: NOS	Injury, poisoning and procedural complications	RTOG Acute RT Morb.	Non-systematic Assessment	EG00046 affected382 at risk EG00134 affected374 at risk
Neurologic: NOS	Nervous system disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00023 affected382 at risk EG00126 affected374 at risk
Acute RT Toxicity: Bladder: NOS	Renal and urinary disorders	Coop. Group CTC	Systematic Assessment	EG000188 affected382 at risk EG001165 affected374 at risk
Bladder/GU: NOS	Renal and urinary disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG000232 affected382 at risk EG001222 affected374 at risk
Gynecomastia: NOS	Reproductive system and breast disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG000266 affected382 at risk EG00142 affected374 at risk
Impotence: NOS	Reproductive system and breast disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00046 affected382 at risk EG00137 affected374 at risk
Skin-general: NOS	Skin and subcutaneous tissue disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00049 affected382 at risk EG00115 affected374 at risk
Hot flashes: NOS	Vascular disorders	RTOG Acute RT Morb.	Non-systematic Assessment	EG00083 affected382 at risk EG00167 affected374 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Title	Description
BG000	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)
BG001	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Radiation therapy (64.8 Gy) + placebo (daily 2 years)			84	382	346	382
EG001	Bicalutamide	Radiation therapy (64.8 Gy) + bicalutamide (150 mg daily 2 years)			97	374	374	374

ID	Type	Description	Link
CDR0000065158
RTOG-R9601