Prostate Cancer
Conditions
Keywords
Prostate Cancer, Hormone Refractory, Metastatic, Localized, Locally Advanced, Prostate Cancer - High Risk Localized or Locally Advanced
Brief summary
This randomized study is looking at the benefits of using docetaxel (chemotherapy) added to one of the standard treatments (radiation and hormones) for men with high-risk prostate cancer.
Detailed description
Radiation therapy plus six months of hormone therapy is one standard way of treating men with high-risk prostate cancer. In this study, we want to see whether or not adding the chemotherapy drug docetaxel (Taxotere)will make this treatment more effective. Docetaxel has shown a benefit in median survival when given to men who have become resistant to hormonal therapy and in men who have metastatic prostate cancer (spread to other areas of the body).
Interventions
DRUGDocetaxel
60 mg/m² q 3 weeks for 3 cycle at the start of treatment followed by weekly Docetaxel at 20 mg/m² per week beginning at week one of radiation therapy and continuing for seven weeks.
DRUGAndrogen Hormonal Suppression and Radiation
Total Androgen Ablation and external beam radiation therapy
DRUGAndrogen Suppression Therapy and Radiation Therapy
Total Androgen Ablation and External Beam Radiation Therapy
Sponsors
Sanofi
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Biopsy proven prostate cancer * Clinical Tumor Category T1b, T1c, T2a and PSA greater than (\>) 10 or Gleason score equal or greater than 4+3=7 or PSA velocity \> 2.0 ng/ml per year and also eligible patients with tumor category T2c, T3a, T3b, or T4 as per 2002 AJCC guidelines. Any minor tertiary grade of Gleason 5; Biopsy Proven or Radiographic (erMRI Seminal Vesicle Invasion); Gleason = or \> 3+4=7 with 50% or more cores positive * Negative bone scan * Lymph node assessment by CT or MR * Adequate hematologic function (Blood Counts) * Adequate liver functions (blood tests) * ECOG performance Status 0 or 1 * Peripheral neuropathy must be =\< grade 1 * PSA obtained within 3 months of entry
Exclusion criteria
* Prior history of malignancy that are \< 5 years except for cancers found to be in-situ and would not likely impact a patient's life expectancy with appropriate medical management. * Prior pelvic radiation therapy * Prior hormonal therapy (up to 4 weeks prior to enrollment allowed) * Individuals unable to tolerate lying still 5 - 10 minutes * Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 90.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 10-Year Restricted Mean Survival Time for Overall Survival | Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years. | Overall survival (OS) was measured from the date of random assignment to death from any cause, censored at the date of last follow-up in surviving patients. The 10-Year Restricted Mean Survival Time was calculated as the area under the Kaplan Meier plot for OS, from randomization to 10-years follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 10-year Biochemical Recurrence (PSA Failure) | PSA was measured following the end of RT, then every 6 months for 5 years and annually thereafter, 10 years | Time to biochemical recurrence was defined as the time from date of random assignment to the earliest of PSA failure or initiation of salvage therapy, or censored at the date of last disease assessment for those without PSA failure. PSA failure was defined according to the 2006 RTOG-ASTRO Phoenix definition (i.e., A PSA rise by 2 ng/mL or more above the nadir). 10-year biochemical recurrence rate was estimated from a competing risk model where non-prostate cancer death was counted as competing risk. |
| 10-year Prostate Cancer Mortality | Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years. | Measured from the date of random assignment to date of death from prostate cancer, or censored at the date of last follow-up in surviving patients. Patients who died due to other reasons were counted as competing risk in a competing risk model. |
| Number of Participants With Acute Adverse Events | During study treatment or within 30 days of the last dose of study, up to 7.2 months from randomization | Adverse acute events were reported via the clinical database only for toxicities considered reportable via the SAE mechanism (those of grade 2 and grade 3 events that are unexpected and possibly, probably, or definitely related/associated with treatment; or all grade 4 and grade 5 events). Common Toxicity Criteria Volume 3.0 (CTCAE) is used for this study. |
| Number of Participants With Late Adverse Events, Any Grade and Attribution | Every 6 months post radiation therapy for 5 years (+/-90 days), then annually, up to 13.9 years from randomization | Late adverse events will be focused on GU/GI including Urinary/Fecal Incontinence, Hematuria, Diarrhea, Rectal Bleeding and other. |
Countries
United States
Participant flow
Recruitment details
9/21/2005 to 1/13/2015
Participants by arm
| Arm | Count |
|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy Androgen Suppression Therapy + Radiation therapy
Weeks 1-9: total androgen suppression Weeks 10-17: total androgen suppression and external beam radiation Weeks 18-26: total androgen suppression | 175 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy Docetaxel + Androgen Suppression Therapy + Radiation Therapy
Weeks 1-9: total androgen suppression and docetaxel 60 mg/m2/q3 weeks x 3 cycles Weeks 10-17: total androgen suppression + external beam radiation therapy + docetaxel 20 mg/m2/week beginning at week 10 x 7 cycles Weeks 18-26: total androgen suppression | 175 |
| Total | 350 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 |
| Overall Study | Delayed Radiation Therapy | 1 | 0 |
| Overall Study | Patient could not tolerate docetaxel | 0 | 2 |
| Overall Study | Patient didn't start due to diagnosis of colon cancer | 0 | 1 |
| Overall Study | Patient didn't start due to low platelet counts | 0 | 1 |
| Overall Study | Patient stopped due to bilateral ruptured tendons | 0 | 1 |
| Overall Study | Patient stopped due to depression | 0 | 1 |
| Overall Study | Physician Decision | 3 | 1 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 5 |
Baseline characteristics
| Characteristic | Arm1: Androgen Suppression Therapy + Radiation Therapy | Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | Total |
|---|---|---|---|
| Age, Continuous | 66 years | 66 years | 66 years |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 29 Participants | 37 Participants | 66 Participants |
| Race/Ethnicity, Customized White | 139 Participants | 132 Participants | 271 Participants |
| Region of Enrollment Australia | 62 Participants | 69 Participants | 131 Participants |
| Region of Enrollment New Zealand | 3 Participants | 4 Participants | 7 Participants |
| Region of Enrollment United States | 110 Participants | 102 Participants | 212 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 175 Participants | 175 Participants | 350 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 45 / 175 | 44 / 175 |
| other Total, other adverse events | 128 / 174 | 142 / 171 |
| serious Total, serious adverse events | 63 / 174 | 87 / 171 |
Outcome results
Primary
10-Year Restricted Mean Survival Time for Overall Survival
Overall survival (OS) was measured from the date of random assignment to death from any cause, censored at the date of last follow-up in surviving patients. The 10-Year Restricted Mean Survival Time was calculated as the area under the Kaplan Meier plot for OS, from randomization to 10-years follow-up
Time frame: Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 10-Year Restricted Mean Survival Time for Overall Survival | 8.82 years | Standard Error 0.19 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 10-Year Restricted Mean Survival Time for Overall Survival | 9.11 years | Standard Error 0.15 |
Secondary
10-year Biochemical Recurrence (PSA Failure)
Time to biochemical recurrence was defined as the time from date of random assignment to the earliest of PSA failure or initiation of salvage therapy, or censored at the date of last disease assessment for those without PSA failure. PSA failure was defined according to the 2006 RTOG-ASTRO Phoenix definition (i.e., A PSA rise by 2 ng/mL or more above the nadir). 10-year biochemical recurrence rate was estimated from a competing risk model where non-prostate cancer death was counted as competing risk.
Time frame: PSA was measured following the end of RT, then every 6 months for 5 years and annually thereafter, 10 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 10-year Biochemical Recurrence (PSA Failure) | 48 percentage of subjects |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 10-year Biochemical Recurrence (PSA Failure) | 54 percentage of subjects |
Secondary
10-year Prostate Cancer Mortality
Measured from the date of random assignment to date of death from prostate cancer, or censored at the date of last follow-up in surviving patients. Patients who died due to other reasons were counted as competing risk in a competing risk model.
Time frame: Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 10-year Prostate Cancer Mortality | 11 percentage of subjects |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 10-year Prostate Cancer Mortality | 15 percentage of subjects |
Secondary
Number of Participants With Acute Adverse Events
Adverse acute events were reported via the clinical database only for toxicities considered reportable via the SAE mechanism (those of grade 2 and grade 3 events that are unexpected and possibly, probably, or definitely related/associated with treatment; or all grade 4 and grade 5 events). Common Toxicity Criteria Volume 3.0 (CTCAE) is used for this study.
Time frame: During study treatment or within 30 days of the last dose of study, up to 7.2 months from randomization
Population: Adverse acute events were evaluated in patients who received at least one dose of protocol treatment (174 out of 175 subjects in Arm1, 171 out of 175 subjects in Arm2).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | Number of Participants With Acute Adverse Events | 18 Participants |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | Number of Participants With Acute Adverse Events | 46 Participants |
Secondary
Number of Participants With Late Adverse Events, Any Grade and Attribution
Late adverse events will be focused on GU/GI including Urinary/Fecal Incontinence, Hematuria, Diarrhea, Rectal Bleeding and other.
Time frame: Every 6 months post radiation therapy for 5 years (+/-90 days), then annually, up to 13.9 years from randomization
Population: Adverse late event was evaluated in patients who received at least one dose of protocol treatment (174 out of 175 subjects in Arm1, 171 out of 175 subjects in Arm2).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | Number of Participants With Late Adverse Events, Any Grade and Attribution | 128 Participants |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | Number of Participants With Late Adverse Events, Any Grade and Attribution | 140 Participants |