Radiation Therapy in Treating Patients With Stage II or Stage III Prostate Cancer

Phase II Trial Of Combined High Dose Rate Brachytherapy And External Beam Radiotherapy For Adenocarcinoma Of The Prostate

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00091390

Enrollment

129

Registered

2004-09-09

Start date

2004-07-31

Completion date

2016-12-31

Last updated

2020-08-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer

Brief summary

RATIONALE: Radiation therapy uses high-energy x-rays and other sources to damage tumor cells. Internal radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving radiation therapy in different ways may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving internal radiation therapy together with external-beam radiation therapy works in treating patients with stage II or stage III prostate cancer.

Detailed description

OBJECTIVES: Primary * Determine the rate of late grade 3 or greater genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and high-dose rate brachytherapy in patients with stage II or III adenocarcinoma of the prostate. Secondary * Determine acute grade 3 or greater genitourinary and gastrointestinal toxicity in patients treated with this regimen. * Determine freedom from biochemical failure in patients treated with this regimen. * Determine overall survival of patients treated with this regimen. * Determine disease-specific survival of patients treated with this regimen. * Determine clinical relapse (local and/or distant) in patients treated with this regimen. * Develop a quality assurance process for high-dose rate prostate brachytherapy. OUTLINE: This is a multicenter study. Patients are stratified according to prostate-specific antigen (≤ 10 ng/mL vs 11-20 ng/mL), T stage (T1c-T2c vs T3a-T3b), combined Gleason score (2-6 vs 7 vs 8-10), prior hormonal therapy (no vs yes), and timing of high-dose rate brachytherapy (before external beam radiotherapy vs after external beam radiotherapy). Patients are followed at 3, 7, 9, and 12 months, every 6 months for 5 years, and then annually thereafter.

Interventions

RADIATIONHigh Dose brachytherapy boost

19 Gy in two fractions (on day of placement and 6-24 hours later) before or after external beam radiotherapy, such that all study treatment occurs within 8 weeks.

RADIATIONExternal beam radiotherapy

45 Gy as 1.8 Gy five days a week for five weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Histologically confirmed, adenocarcinoma of the prostate, clinical stage T1c-T3b, N0, M0. 2. Patient will have clinically negative nodes as established by imaging (pelvic computed tomography (CT), magnetic resonance imaging (MRI)). 3. The patient will be clinically M0. 4. Zubrod status 0-1. 5. No prior pelvic or prostate radiation or chemotherapy for prostate cancer; induction hormonal therapy beginning ≤ 120 days prior to registration is acceptable. 6. One of the following combinations of factors: Clinical stage T1c-T2c, Gleason score 2-6 and prostate-specific antigen (PSA) \>10 but ≤ 20 Clinical stage T3a-T3b, Gleason score 2-6 and PSA ≤ 20 Clinical stage T1c-T3b, Gleason score 7-10 and PSA ≤ 20 7. Patients must sign a study-specific consent form prior to registration.

Exclusion criteria

1. Stage T4 disease. 2. Lymph node involvement (N1). 3. Evidence of distant metastases (M1). 4. Radical surgery for carcinoma of the prostate. 5. Previous hormonal therapy beginning \> 120 days prior to registration. 6. Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up. 7. Prior transurethral resection of the prostate (TURP). 8. Prior invasive malignancy(except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the oral cavity or bladder are permissible). 9. Hip prosthesis.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Late Grade 3-5 Genitourinary (GU) and Gastrointestinal (GI) Adverse Events (AE) at 18 Months	From 9 to 18 months after start of study treatment	Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Late is defined as occurring after 9 months from the start of study treatment. Because of the lead time of 9 months, the percentage at 18-months was estimated by the 9-month rate using the cumulative incidence method starting at the 10th month. Death was treated as a competing risk.

Secondary

Measure	Time frame	Description
Percentage of Participants With Biochemical Failure at 10 Years Using American Society for Therapeutic Radiation and Oncology (ASTRO) Definition	From registration to ten years	The ASTRO criteria for biochemical failure is three consecutive rises in prostate-specific antigen (PSA) level above the nadir after radiation therapy. The PSA nadir is defined as as the lowest PSA value reached immediately before a biochemical failure. The date of failure is midway between the last non-rising PSA and the first rise in PSA. Time to failure is defined as time from registration to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rate is estimated using the cumulative incidence method.
Percentage of Participants With Biochemical Failure at 10 Years Using the Phoenix Definition	From registration to ten years	The Phoenix criteria for biochemical failure is a rise of 2 ng/mL or more above the nadir after radiation therapy. Time to failure is defined as time from registration to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rate is estimated using the cumulative incidence method.
Percentage of Participants Alive at 10 Years	From registration to 10 years	Overall survival time is defined as time from registration to the date of death from any cause or last known follow-up (censored). Overall survival rate is estimated by the Kaplan-Meier method.
Number of Participants With Acute Grade 3-5 Genitourinary (GU) and Gastrointestinal (GI) Adverse Events (AE)	From treatment start to 9 months	Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Acute is defined as occurring within 9 months from the start of study treatment.
Percentage of Participants With Distant Failure at 10 Years	From registration to ten years	Distant failure required documentation of regional nodal recurrence or distant disease relapse. Time to failure is defined as time from registration to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rate is estimated using the cumulative incidence method.
Percentage of Participants With Local Failure at 10 Years	From registration to ten years	Local failure is defined as documented local progression as determined by clinical exam. Time to failure is defined as time from registration to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rate is estimated using the cumulative incidence method.
Percentage of Participants With Death Due to Prostate Cancer at 10 Years	From registration to ten years	The following will be considered as death due to prostate cancer (failure): * Death certified as due to prostate cancer. * Death from other causes with active malignancy (clinical or biochemical progression). * Death due to complications of treatment, irrespective of the status of malignancy. Time to failure is defined as time from registration to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rate is estimated using the cumulative incidence method.

Countries

United States

Participant flow

Participants by arm

Arm	Count
External Beam Radiotherapy and High Dose Brachytherapy Boost High Dose brachytherapy boost: 19 Gy in two fractions (on day of placement and 6-24 hours later) before or after external beam radiotherapy, such that all study treatment occurs within 8 weeks. External beam radiotherapy: 45 Gy as 1.8 Gy five days a week for five weeks.	125
Total	125

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	No protocol treatment	3
Overall Study	Protocol Violation	1

Baseline characteristics

Characteristic	External Beam Radiotherapy and High Dose Brachytherapy Boost
Age, Continuous	68 years
Baseline Prostate-Specific Antigen (PSA) ≤10	87 Participants
Baseline Prostate-Specific Antigen (PSA) >10 - ≤20	38 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants
Gleason score 2-6	13 Participants
Gleason score 7	90 Participants
Gleason score 8-10	22 Participants
Prior hormone therapy No	71 Participants
Prior hormone therapy Yes	54 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	32 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	86 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	125 Participants
T Stage T1c-T2c	114 Participants
T Stage T3a-T3b	11 Participants
Zubrod Performance Scale 0 (Asymptomatic)	121 Participants
Zubrod Performance Scale 1 (Symptomatic but completely ambulatory)	4 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	110 / 115
serious Total, serious adverse events	49 / 115

Outcome results

Primary

Percentage of Participants With Late Grade 3-5 Genitourinary (GU) and Gastrointestinal (GI) Adverse Events (AE) at 18 Months

Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Late is defined as occurring after 9 months from the start of study treatment. Because of the lead time of 9 months, the percentage at 18-months was estimated by the 9-month rate using the cumulative incidence method starting at the 10th month. Death was treated as a competing risk.

Time frame: From 9 to 18 months after start of study treatment