Prostate Cancer
Conditions
Keywords
Prostate Cancer, Radical prostatectomy
Brief summary
There is a high relapse rate for patients who have undergone prostatectomy and have pathologic extracapsular prostate extension, positive surgical margins or seminal vesicle involvement (pathologic stage 3 disease). While adjuvant radiation improves progression-free and overall survival, approximately half of these patients will develop recurrence. Similarly, radiation therapy has become the standard salvage therapy for patients with rising PSA \>0.1 - \< 2.0 ng/mL. In common solid tumors such as NSCLC, head and neck cancer and upper gastrointestinal cancers, the addition of chemotherapy to radiation improves survival. It is hypothesized that the addition of radiosensitizing chemotherapy to standard adjuvant radiation will improve survival in patients with stage 3 prostate cancer after prostatectomy and patients with rising PSA \< 2.0 ng.mL without detectable disease. Taxanes are powerful radiation enhancers since they synchronize tumor cells in G2/M the most radiosensitive phase of the cell cycle.17,18 Cabazitaxel is the most active taxane in the treatment of prostate cancer. Therefore, we propose a phase I study establishing the optimal dose of cabazitaxel with adjuvant radiation for stage 3 prostate cancer after prostatectomy (PSA undetectable - \< 2.0 ng/mL). and for patients with persistent or rising PSA post prostatectomy (PSA \>0.1 - \< 2.0 ng/mL).
Interventions
DRUGCabazitaxel
Dose Level Day 1, 22, 43 1. 5.0 mg/m2 2. 10.0 mg/m2 3. 15.0 mg/m2 4. 20.0 mg/m2
Sponsors
Brown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Conditions for Patient Eligibility Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Radical prostatectomy for adenocarcinoma of the prostate with at least one of the following: * Extracapsular tumor extension, * Positive surgical margins, * Seminal vesicle invasion * Regional lymph node positive (N1) * Post-prostatectomy PSA of \> 0.1 - \< 2.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration in a patient with T2 or T3 disease at prostatectomy. * No distant metastases. * No prior pelvic or prostate radiation or chemotherapy for prostate cancer. * ECOG performance status 0-1. * Age\>18. * Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥ 1500 cells/mm3; platelet count ≥100,000 cells/mm3, Creatinine ≤ 1.5X upper limit of normal (if creatinine clearance 1.0-1.5x ULN, creatinine clearance will be calculated according to Chronic Kidney Disease Epidemiology Group formula and patients with creatinine clearance \< 60 ml/min should be excluded),19 .Hgb \> 9.0 g/dl, total bilirubin ≤ 1x ULN, and AST or ALT ≤ 2.5 x ULN. * Life expectancy of at least 1 year. * Must not have uncontrolled severe, intercurrent illness. * No concurrent anticancer therapy. * Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. * Signed study-specific consent form prior to study entry. * Conditions for Patient Ineligibility Patients meeting any of the following
Exclusion criteria
are not to be enrolled in the study: * Evidence of distant metastases (M1). Equivocal bone scans are allowed if plain films are negative for metastasis. * Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up. * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (For example, carcinoma in situ of the oral cavity or bladder are permissible). * History of severe hypersensitivity (\> grade 3) reaction to Cabazitaxel or other drugs formulated with polysorbate 80. * History of severe hypersensitivity (\> grade 3) to docetaxel. * Any uncontrolled severe, intercurrent illness (including uncontrolled diabetes) * At least 4 weeks since any major surgery. * Patients on concurrent anticancer therapy. * PSA \> 2ng/ml * Concurrent or planned treatment with strong inhibitors or inducers of cytochrome p450 3A4/5 (a one-week wash out period is necessary for patients who are already on these treatments (see appendix H and I) * Androgen deprivation therapy started prior to prostatectomy for \> 6 months duration; * Neoadjuvant chemotherapy prior to prostatectomy; * Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the primary treatment and not a salvage procedure; * Prior pelvic radiotherapy;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Cabazitaxel With Concurrent Adjuvant Radiation | 2 mos | The MTD was not determined secondary to the study closing early. That being said the numbers provided below show that 4 patients were treated on study to aide in the investigation of the MTD. Only 1 dose was fully evaluated which was 5mg/m2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing a Toxicity Associated With Cabazitaxel and Adjuvant Radiation Following Prostatectomy for Patients With Stage 3 Prostate Cancer and for Patients With a PSA Elevation Post-Prostatectomy. | During study treatment (approximately 8 weeks) through 30 days post treatment, approximately 12 weeks. | Assess toxicity using CTCAE version 4.0. Number of patients who experienced a toxicity on the study. Not all toxicities are related to study treatment. Of note, there were no serious adverse events on this trial. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cabazitaxel and Radiation Radiation therapy (RT) will be delivered to 64.8 Gy, using IMRT treatment Cabazitaxel will be administered IV every 21 days for 3 doses at the assigned dose level.
Cabazitaxel: Dose Level Day 1, 22, 43
1. 5.0 mg/m2
2. 10.0 mg/m2
3. 15.0 mg/m2
4. 20.0 mg/m2 | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Cabazitaxel and Radiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 61 years |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Maximum Tolerated Dose of Cabazitaxel With Concurrent Adjuvant Radiation
The MTD was not determined secondary to the study closing early. That being said the numbers provided below show that 4 patients were treated on study to aide in the investigation of the MTD. Only 1 dose was fully evaluated which was 5mg/m2
Time frame: 2 mos
Population: while 5 participants were enrolled only 4 completed treatment as patients # 5 only received part of day 1 therapy secondary to an AE and therefore is not included in the assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cabazitaxel and Radiation | Maximum Tolerated Dose of Cabazitaxel With Concurrent Adjuvant Radiation | NA mg/m2 |
Secondary
Number of Participants Experiencing a Toxicity Associated With Cabazitaxel and Adjuvant Radiation Following Prostatectomy for Patients With Stage 3 Prostate Cancer and for Patients With a PSA Elevation Post-Prostatectomy.
Assess toxicity using CTCAE version 4.0. Number of patients who experienced a toxicity on the study. Not all toxicities are related to study treatment. Of note, there were no serious adverse events on this trial.
Time frame: During study treatment (approximately 8 weeks) through 30 days post treatment, approximately 12 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cabazitaxel and Radiation | Number of Participants Experiencing a Toxicity Associated With Cabazitaxel and Adjuvant Radiation Following Prostatectomy for Patients With Stage 3 Prostate Cancer and for Patients With a PSA Elevation Post-Prostatectomy. | 5 Participants |