Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer
Brief summary
RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with prostate cancer.
Detailed description
OBJECTIVES: Primary * To escalate the dose of stereotactic body radiotherapy (SBRT) to a tumoricidal dose without exceeding the maximum tolerated dose in patients with organ-confined prostate cancer. (Phase I) * To determine the late, severe grade 3-5 genitourinary and gastrointestinal toxicity occurring between 270-540 days (i.e., 9-18 months) from the start of the protocol treatment as assessed by CTCAE v3.0. (Phase II) Secondary * To determine the dose-limiting toxicity of SBRT in these patients. (Phase I) * To determine the 2-year biochemical (PSA) control (freedom from PSA failure), disease-free and overall survival, local control, freedom from distant metastases, and the incidence of high-grade adverse events of any type in patients treated with this therapy in order to determine if the therapy is promising enough for further clinical investigation. (Phase II) OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II open-label study. * Phase I: Patients undergo 5 treatments of stereotactic body radiotherapy (SBRT). * Phase II: Patients undergo SBRT at the maximum tolerated dose as in phase I. After completion of study treatment, patients are followed at 1.5, 3, 6, 9, and 12 months, every 6 months for 5 years, and then once a year for years 5-10. PROJECTED ACCRUAL: A total of 97 patients will be accrued for this study.
Interventions
RADIATIONstereotactic body radiation therapy (SBRT)- 45 Gy
Dose of SBRT - 45 Gray (Gy) in five fractions
RADIATIONstereotactic body radiation therapy (SBRT) - 47.5 Gy
Dose of SBRT - 47.5 Gray (Gy) in five fractions
RADIATIONstereotactic body radiation therapy (SBRT) - 50 Gy (Phase 1)
RADIATIONstereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2)
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate * Stage T1a, T1b, T1c disease * Stage T2a or T2b * No direct evidence of regional or distant metastases * No T2c, T3, or T4 tumors * Gleason score ≤ 7 * Must meet the following criteria: * Prostate-specific antigen (PSA) ≤ 20 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 2-6 * PSA ≤ 15 ng/mL prior to starting hormonal therapy (if given) for patients with a Gleason score of 7 * Risk of pelvic lymph node involvement \< 20% according to Roach formula * Ultrasound-based volume estimation of the prostate gland ≤ 60 g PATIENT CHARACTERISTICS: * Zubrod performance status 0-2 * Fertile patients must use effective contraception * No prior invasive malignancy, except for nonmelanoma skin cancer, unless disease-free for a minimum of 3 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are allowed) * No significant urinary obstructive symptoms * American Urological Association (AUA) score of ≤ 15 (alpha blockers allowed) * No history of inflammatory colitis (including Crohn disease and ulcerative colitis) * No history of significant psychiatric illness * No severe, active comorbidity including 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 at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Laboratory tests for liver function and coagulation parameters are not required for entry into this protocol * AIDS (based on current CDC definition) or other immunocompromising condition * HIV testing is not required for entry into this protocol PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 9 months since prior hormonal therapy as neoadjuvant therapy or to downsize the prostate gland * No prior pelvic radiotherapy * No prior chemotherapy or surgery for prostate cancer * No prior transurethral resection of the prostate (TURP) or cryotherapy to the prostate * No plans for other concurrent post-treatment, adjuvant, antineoplastic therapy including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy as part of the treatment for prostate cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | 90 days after start of treatment | Dose-limiting toxicity (DLT) was defined as grade 3 to 5 GI, genito urinary, sexual, or neurologic toxicity attributed to therapy occurring within 90 days of registration using Common Terminology Criteria of Adverse Events(version 3) |
| No. of Late Severe GU Toxicity (for Phase 2 Only) | 18 months | To determine late severe GU toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
| No. of Late Severe GI Toxicity (for Phase 2 Only) | 18 months | To determine late severe GI toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-GU Toxicity | 60 months | To determine non-GU (genitourinary) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
| Non-GI Toxicity | 60 months | To determine non-GI (gastrointestinal) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
| GU Toxicity (Only Phase 2) | 9 months from start of treatment | To determine acute severe GU toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
| Disease Specific Survival | 60 months | Disease-Specific Survival Disease-specific survival will be measured from the date of study entry to the date of death due to prostate cancer as the percentage of participants who survived the prostrate cancer disease. |
| Clinical Progression Including Local/Regional and Distant Relapse | 60 months | Clinical progression including local/regional and distant relapse is measured using Kaplan-Meier method |
| Freedom From Biochemical Failure | 36 months | Biochemical failure RTOG (Radiation Therapy Oncology Group)-ASTRO (American Society for Therapeutic Radiology and Oncology) definition (also known as Phoenix definition). Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached. |
| GI Toxicity | 9 months from start of treatment | To determine acute severe GI toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death. |
| Overall Survival | 60 months | The survival time will be measured from the date of accession to the date of death. |
Countries
United States
Participant flow
Recruitment details
A total of 94 patients were recruited. Two patients withdrew consent before treatment and an additional patient had Gleason 9 disease upon pathology review and was excluded from the analysis. A total of 91 patients were analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: SBRT- 45 Gy(SBRT) 45 Gy. The dose of Stereotactic Body Radiation Therapy (SBRT) is - 45 Gy in Phase 1 | 15 |
| Phase 1: SBRT- 47.5 Gy The dose of Stereotactic Body Radiation Therapy (SBRT) is - 47.5 Gy in Phase 1 | 15 |
| Phase 1: Stereotactic Body Radiation Therapy (SBRT) 50 Gy. The dose of Stereotactic Body Radiation Therapy (SBRT) is - 50 Gy in Phase 1 | 14 |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy The dose of SBRT is escalated- 50 Gy in Phase 2 stereotactic body radiation therapy (SBRT) - 50 Gy (Phase 2). | 47 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1: SBRT- 45 Gy(SBRT) 45 Gy. | Phase 1: SBRT- 47.5 Gy | Phase 1: Stereotactic Body Radiation Therapy (SBRT) 50 Gy. | Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67 years | 67 years | 67 years | 65 years | 66 years |
| Race/Ethnicity, Customized Non-White | 6 Participants | 2 Participants | 2 Participants | 15 Participants | 25 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 13 Participants | 12 Participants | 32 Participants | 66 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 14 Participants | 47 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 15 | 2 / 15 | 1 / 14 | 1 / 47 |
| other Total, other adverse events | 8 / 15 | 8 / 15 | 11 / 14 | 33 / 47 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 14 | 0 / 47 |
Outcome results
Primary
No. of Late Severe GI Toxicity (for Phase 2 Only)
To determine late severe GI toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: SBRT- 45 Gy | No. of Late Severe GI Toxicity (for Phase 2 Only) | Grade III | 4 participants |
| Phase 1: SBRT- 45 Gy | No. of Late Severe GI Toxicity (for Phase 2 Only) | Grade IV | 2 participants |
| Phase 1: SBRT- 45 Gy | No. of Late Severe GI Toxicity (for Phase 2 Only) | Grade V | 0 participants |
Primary
No. of Late Severe GU Toxicity (for Phase 2 Only)
To determine late severe GU toxicity defined as grade 3-5 occurring between 279-540 days (i.e., 9-18 months) from the start of protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: SBRT- 45 Gy | No. of Late Severe GU Toxicity (for Phase 2 Only) | Grade III | 3 participants |
| Phase 1: SBRT- 45 Gy | No. of Late Severe GU Toxicity (for Phase 2 Only) | Grade IV | 1 participants |
| Phase 1: SBRT- 45 Gy | No. of Late Severe GU Toxicity (for Phase 2 Only) | Grade V | 0 participants |
Primary
Number of Participants With Dose Limiting Toxicity (Phase 1 Only)
Dose-limiting toxicity (DLT) was defined as grade 3 to 5 GI, genito urinary, sexual, or neurologic toxicity attributed to therapy occurring within 90 days of registration using Common Terminology Criteria of Adverse Events(version 3)
Time frame: 90 days after start of treatment
Population: Total enrolled was 47 patients to the phase I study, although two withdrew consent before treatment and an additional patient had Gleason 9 disease upon pathology and was excluded from the analysis. MTD not met in Phase I.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: SBRT- 45 Gy | Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | 0 participants |
| Phase 1: SBRT- 47.5 Gy | Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | 0 participants |
| Phase 1: SBRT- 50 Gy | Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | 0 participants |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Number of Participants With Dose Limiting Toxicity (Phase 1 Only) | 0 participants |
Secondary
Clinical Progression Including Local/Regional and Distant Relapse
Clinical progression including local/regional and distant relapse is measured using Kaplan-Meier method
Time frame: 60 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: SBRT- 45 Gy | Clinical Progression Including Local/Regional and Distant Relapse | 1 number of participants |
| Phase 1: SBRT- 47.5 Gy | Clinical Progression Including Local/Regional and Distant Relapse | 0 number of participants |
| Phase 1: SBRT- 50 Gy | Clinical Progression Including Local/Regional and Distant Relapse | 0 number of participants |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Clinical Progression Including Local/Regional and Distant Relapse | 0 number of participants |
Secondary
Disease Specific Survival
Disease-Specific Survival Disease-specific survival will be measured from the date of study entry to the date of death due to prostate cancer as the percentage of participants who survived the prostrate cancer disease.
Time frame: 60 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: SBRT- 45 Gy | Disease Specific Survival | 100 percentage of participants |
| Phase 1: SBRT- 47.5 Gy | Disease Specific Survival | 100 percentage of participants |
| Phase 1: SBRT- 50 Gy | Disease Specific Survival | 100 percentage of participants |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Disease Specific Survival | 100 percentage of participants |
Secondary
Freedom From Biochemical Failure
Biochemical failure RTOG (Radiation Therapy Oncology Group)-ASTRO (American Society for Therapeutic Radiology and Oncology) definition (also known as Phoenix definition). Thus, when the PSA rises by more than 2 ng/ml above the lowest level (nadir) achieved after treatment, biochemical failure has occurred and the date of the failure is recorded at the time the nadir plus 2 ng/ml level is reached.
Time frame: 36 months
Population: Phase 1: SBRT- 45Gy was the only arm to have a patient with biochemical progression.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: SBRT- 45 Gy | Freedom From Biochemical Failure | 90.9 percentage of participants |
| Phase 1: SBRT- 47.5 Gy | Freedom From Biochemical Failure | 100 percentage of participants |
| Phase 1: SBRT- 50 Gy | Freedom From Biochemical Failure | 100 percentage of participants |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Freedom From Biochemical Failure | 100 percentage of participants |
Secondary
GI Toxicity
To determine acute severe GI toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 9 months from start of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: SBRT- 45 Gy | GI Toxicity | Grade III | 1 participants |
| Phase 1: SBRT- 45 Gy | GI Toxicity | Grade IV | 1 participants |
| Phase 1: SBRT- 45 Gy | GI Toxicity | Grade V | 0 participants |
Secondary
GU Toxicity (Only Phase 2)
To determine acute severe GU toxicity is defined as grade 3-5 occurring prior to 270 days from the start of the protocol treatment. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 9 months from start of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: SBRT- 45 Gy | GU Toxicity (Only Phase 2) | Grade III | 0 participants |
| Phase 1: SBRT- 45 Gy | GU Toxicity (Only Phase 2) | Grade IV | 0 participants |
| Phase 1: SBRT- 45 Gy | GU Toxicity (Only Phase 2) | Grade V | 0 participants |
Secondary
Non-GI Toxicity
To determine non-GI (gastrointestinal) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 60 months
Population: The data was not collected.
Secondary
Non-GU Toxicity
To determine non-GU (genitourinary) toxicity is defined as grade 3-5. Toxicity was defined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0. CTCAE uses a range of grades from 1 to 5; 1 - Mild 2 - Moderate 3 - Severe 4 - Life-threatening 5 - Death.
Time frame: 60 months
Population: The data was not collected.
Secondary
Overall Survival
The survival time will be measured from the date of accession to the date of death.
Time frame: 60 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: SBRT- 45 Gy | Overall Survival | 71.5 percentage of participants |
| Phase 1: SBRT- 47.5 Gy | Overall Survival | 85 percentage of participants |
| Phase 1: SBRT- 50 Gy | Overall Survival | 92 percentage of participants |
| Phase 2: Stereotactic Body Radiation Therapy (SBRT)- 50 Gy | Overall Survival | 98 percentage of participants |