Prostate Cancer
Conditions
Keywords
prostatectomy, androgen deprivation, chemotherapy, radiation
Brief summary
To assess the safety of treating men with oligometastatic prostate cancer with the following therapy: (1st) Systemic chemo-hormonal therapy with up to 6-months (\ 24 weeks) of adjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 2 years of androgen deprivation. Androgen blockade will be the same throughout the course of treatment.
Detailed description
Adjuvant treatment (month 1 through \ 6): All patients will be treated with up to 6 months of androgen deprivation, plus up to 6 cycles of docetaxel chemotherapy. Following docetaxel therapy, patients with a Prostate-specific antigen response of at least a 50% decrease from baseline, will proceed to maximum consolidative therapy. Radiation (month 7 though \ 11): After completion of adjuvant chemotherapy, the men will be treated with definitive local therapy with adjuvant radiation therapy (RT). After definitive local therapy, patients will be treated with consolidative stereotactic body radiation therapy (SBRT) to the metastatic sites (if present). Follow up: Patients will continue on androgen deprivation for a total of 2 years. They will be followed clinically and monitored with serum testosterone and Prostate-specific antigen until 2-years after completion of ADT (Androgen deprivation therapy) treatment. Androgen blockade will be the same throughout the course of treatment.
Interventions
DRUGLeuprolide Acetate
22.5mg by intramuscular (IM) injection every 3 months
DRUGDocetaxel
75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles. Dose may decreased in the following intervals: 65 mg/M2, 55 mg/M2, 35 mg/M2.
DRUGBicalutamide
bicalutamide (Casodex) 50mg by mouth daily
RADIATIONRadiation
Radiation will be delivered in 1 to 5 fractions, and the dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints in accordance with AAPM Task Group 101 recommendations. Typical doses include 16 - 24 Gy in 1 fraction, 48 - 50 Gy in 4 fractions, and 50 - 60 Gy in 5 fractions.
DRUGAbiraterone Acetate
Abiraterone acetate 1000 mg / day may be given at the investigator's discretion.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent. 2. Age ≥ 18 years 3. Eastern cooperative oncology group (ECOG) performance status ≤2 4. Documented histologically confirmed adenocarcinoma of the prostate 5. Willing to undergo the following therapy: (1st) Systemic chemo-hormonal therapy with up to 6-months (\ 24 weeks) of neoadjuvant androgen deprivation and up to 6 cycles of chemotherapy, (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. Additionally, must be willing to be treated with a full two years of androgen deprivation. 6. Oligometastatic prostate cancer: Stage T1-4, N0-1 and/or M1a-b (up to 5 metastatic lesions- including bone lesions and non-regional lymph nodes seen on bone scan, contrast enhanced CT scan, or positron emission tomography PET scan)
Exclusion criteria
1. Prior local non-surgical therapy to treat prostate cancer (e.g. radiation therapy, brachytherapy) 2. Prior therapy to a metastatic site. 3. Prior or ongoing systemic therapy for prostate cancer including, but not limited to: 1. Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix) 2. CYP-17 (cytochrome P450 17α-hydroxy/17,20-lyase) inhibitors (e.g. ketoconazole) 3. Antiandrogens (e.g. bicalutamide, nilutamide) 4. Second generation antiandrogens (e.g. enzalutamide, abiraterone) 5. Immunotherapy (e.g. sipuleucel-T, ipilimumab) 6. Chemotherapy (e.g. docetaxel, cabazitaxel) \*Note: may be enrolled if hormone therapy was recently initiated (\<90 days duration)). In the event that hormone therapy was initiated prior to study enrollment, the clock for 2 years of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment. 4. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study. 5. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule. 6. Abnormal bone marrow function \[absolute neutrophil count (ANC)\<1500/mm3, platelet count \<100,000/mm3, hemoglobin \<9 g/dL\] 7. Abnormal liver function (bilirubin \>ULN ( upper limit of normal); AST (aspartate aminotransferase), ALT (alanine transaminase) \> 2.5 x upper limit of normal) 8. Creatinine clearance of ≥ 30 mL/min. CrCl (Creatinine clearance) should be calculated suing the Cockcroft-Gault formula. 9. Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within previous six months. 10. Prior history of malignancy in the past 3 years with the exception of basal cell and squamous cell carcinoma of the skin. Other malignancies that are considered to have a low potential to progress may be enrolled at discretion of PI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate | 3 years | To evaluate efficacy of multimodality therapy in men, defined as the 3 year Prostate-specific antigen progression-free (Prostate-specific antigen\<0.2 ng/ml) survival rate among men who have non-castrate testosterone levels 2 years after enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification | 3 years | To assess the safety of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer after prostatectomy. Toxicities related to neoadjuvant therapy, radiation therapy, or stereotactic body radiation therapy (SBRT) will be assessed using CTCAE version 4 criteria. Surgical toxicities will be assessed using the Clavien-Dindo Classification |
| Time to Prostate-specific Antigen Recurrence | 3 years | To investigate the time from an undetectable Prostate-specific antigen (≤0.2 ng/mL) until the Prostate-specific antigen is \>0.2 over two time-points. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemohormonal and Definitive Therapy After Prostatectomy (1st) Systemic chemo-hormonal therapy with up to 6-months (\
24 weeks) of adjuvant androgen deprivation (Leuprolide Acetate) and up to 6 cycles of chemotherapy (Docetaxel), (2nd) definitive local tumor control with adjuvant radiation therapy, and (3rd) consolidative stereotactic radiation to oligometastatic lesions. The men will receive a total of 2 years of androgen deprivation. Androgen blockade (Bicalutamide) will be the same throughout the course of treatment.
Leuprolide Acetate: 22.5mg by intramuscular (IM) injection every 3 months
Docetaxel: 75 mg/m2 IV will be given on day 1 every 3 weeks, up to 6 cycles. Dose may decreased in the following intervals: 65 mg/M2, 55 mg/M2, 35 mg/M2.
Bicalutamide: bicalutamide (Casodex) 50mg by mouth daily
Radiation: Radiation will be delivered in 1 to 5 fractions, and the dose and fractionation schedule will depend on the size and location of the lesion and the surrounding normal tissue constraints in accordance with AAPM Task Group 101 recommendations. Typical doses include 16 - 24 Gy in 1 fraction, 48 - 50 Gy in 4 fractions, and 50 - 60 Gy in 5 fractions.
Abiraterone Acetate: Abiraterone acetate 1000 mg / day may be given at the investigator's discretion. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Chemohormonal and Definitive Therapy After Prostatectomy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 62.2 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 18 Participants |
| Region of Enrollment United States | 26 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 2 / 26 |
Outcome results
Primary
Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate
To evaluate efficacy of multimodality therapy in men, defined as the 3 year Prostate-specific antigen progression-free (Prostate-specific antigen\<0.2 ng/ml) survival rate among men who have non-castrate testosterone levels 2 years after enrollment.
Time frame: 3 years
Population: Assessed 25/26 patients (1 patient withdrew from study prior completing TED)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemohormonal and Definitive Therapy After Prostatectomy | Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate | 3-year Prostate-specific antigen PFS (Prostate-specific antigen <0.2), after enrollment | 22 Participants |
| Chemohormonal and Definitive Therapy After Prostatectomy | Efficacy as Assessed by 3-year Prostate-specific Antigen Progression-free Survival Rate | 3-year Prostate-specific antigen PFS (Prostate-specific antigen >=0.2), after enrollment | 3 Participants |
Secondary
Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification
To assess the safety of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer after prostatectomy. Toxicities related to neoadjuvant therapy, radiation therapy, or stereotactic body radiation therapy (SBRT) will be assessed using CTCAE version 4 criteria. Surgical toxicities will be assessed using the Clavien-Dindo Classification
Time frame: 3 years
Population: Assessed all patients, from time of enrollment until study exit/3 years from enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemohormonal and Definitive Therapy After Prostatectomy | Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification | No Grades 3 and 4 neutropenia and surgical- or radiation-induced toxicities. | 24 Participants |
| Chemohormonal and Definitive Therapy After Prostatectomy | Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification | grade 4 neutropenia | 1 Participants |
| Chemohormonal and Definitive Therapy After Prostatectomy | Safety of the 3 Years Multimodality Therapy Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4 Criteria and the Clavien-Dindo Classification | grade 3 neutropenic fever | 1 Participants |
Secondary
Time to Prostate-specific Antigen Recurrence
To investigate the time from an undetectable Prostate-specific antigen (≤0.2 ng/mL) until the Prostate-specific antigen is \>0.2 over two time-points.
Time frame: 3 years
Population: Assessed 25/26 patients (1 patient withdrew from study prior completing TED)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemohormonal and Definitive Therapy After Prostatectomy | Time to Prostate-specific Antigen Recurrence | NA Month |