Castration-Sensitive Prostate Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Prostate Small Cell Neuroendocrine Carcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8
Conditions
Keywords
Prostate Cancer
Brief summary
This phase II trial studies how well antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy work in treating patients with prostate cancer. Hormone therapy such as antiandrogen therapy may fight prostate cancer by blocking the production and interfering with the action of hormones. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Neutron radiation therapy uses high energy neutrons to kill tumor cells and shrink tumors. It is not yet known whether antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy may work better in treating patients with prostate cancer.
Detailed description
OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 weeks for 6 months.
Interventions
Undergo ADT
DRUGAbiraterone Acetate
Undergo Abiraterone Acetate Treatment SOC
DRUGPrednisone
Undergo Prednisone Treatment SOC
RADIATIONRadiation Therapy
Undergo neutron radiation therapy
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically proven (either histologic or cytologic) diagnosis of prostate adenocarcinoma with \< 50% neuroendocrine differentiation or small cell histology. * At least one site of nodal or distant metastatic disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, or a bony metastasis that is evaluable on both computed tomography (CT) and bone scan. * No prior orchiectomy. * No androgen deprivation therapy such as treatment with antiandrogens, luteinizing hormone-releasing hormone (LHRH) agonists or antagonists for at least one year prior to trial enrollment, and testosterone must be inside normal range prior to trial enrollment if there is prior history of ADT. * No other systemic anti-cancer therapy for at least 1-year prior to enrollment. * Prior prostate-directed therapies such as prostatectomy or cryotherapy are allowed. * Prior radiation treatments are allowed (prostate or metastatic sites) but must have been completed at least 3 months prior to starting ADT for this trial. * White blood cell (WBC) \> 3000/mm\^3. * Absolute neutrophil count (ANC) \> 1000/mm\^3. * Platelets \> 100,000/mm\^3. * Creatinine \< 1.5 institutional upper limit of normal (ULN) or calculated creatinine clearance \> 30 ml/min. * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin \< 3 x institutional ULN (unless patient has documented Gilbert's syndrome). * No steroids for at least 2 weeks prior to enrollment, and patient must not be expected to require steroids during the study period, other than the typical low dose steroid that is given with abiraterone (typically prednisone or prednisolone at 5 mg twice daily). * Zubrod performance status 0-2. * Patient must sign study specific informed consent prior to study entry. * Men who are sexually active must use medically acceptable forms of contraception.
Exclusion criteria
* Other illnesses with a life expectancy of less than 6 months, including but not limited to unstable angina, symptomatic congestive heart failure, cardiac arrhythmias. * Psychological or social issues that would prevent patients from informed consent or complying with study requirements. * Subject has a history of unexplained loss of consciousness or transient ischemic attack within 12 months of treatment start. * Individuals on active treatment for a different cancer are excluded. Individuals with a history of other malignancies are eligible if they are deemed by the investigator to be at low risk for recurrence of that malignancy. * Known brain metastasis. * Known allergies, hypersensitivity, or intolerance to abiraterone or prednisone. * Prior ADT less than a year, or greater than two months, prior to trial enrollment or prior ADT with testosterone less than normal. * There is a potential drug interaction when abiraterone is concomitantly used with a CYP2D6 substrate narrow therapeutic index (e.g., thioridazine, dextromethorphan), or strong CYP3A4 inhibitors (e.g., atazanavir, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) or strong inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine). Caution should be used when patients are on one of these drugs. * Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, human immunodeficiency virus (HIV), or chronic liver disease are not eligible. * Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Peripheral Blood Effector T-cells (CCR7-/CD45RO) | Baseline to 3 months after start of antiandrogen therapy (ADT) | Percent change in peripheral blood effector T-cells will be calculated by measuring the difference of the percent peripheral blood effector T-cells for each patient between two time points: pre-treatment and post-treatment (3 months after start of ADT, which is also 1 month post-radiation in the radiation arm). Unpaired two-sample t-test or Wilcoxon rank-sum test, depending on distribution of the percent change, will be used to test the null hypothesis that the percent change in peripheral blood effector T-cells is equal between the two arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Undetectable Prostate Specific Antigen (PSA) (< 0.2) | At 6 months after start of abiraterone acetate | The number of patients with undetectable PSA at 6-months will be summarized by each arm and all combined. |
| Incidence of Adverse Events | Up to 6 months | Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety and tolerability as evaluated by the incidence, severity, duration, causality, seriousness of adverse events. Toxicities will be summarized as the number of patients with grade 3 or higher toxicities per CTCAE v4.0, in addition to total number of toxicities (allowing for multiple toxicities within a patient) among all patients, and per treatment arm. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (ADT, Abiraterone, Prednisone) Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity.
Antiandrogen Therapy: Undergo ADT
Abiraterone Acetate: Undergo Abiraterone Acetate Treatment SOC
Prednisone: Undergo Prednisone Treatment SOC | 6 |
| Arm II (ADT, Abiraterone, Prednisone, Radiation Therapy) Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.
Antiandrogen Therapy: Undergo ADT
Abiraterone Acetate: Undergo Abiraterone Acetate Treatment SOC
Prednisone: Undergo Prednisone Treatment SOC
Radiation Therapy: Undergo neutron radiation therapy | 4 |
| Total | 10 |
Baseline characteristics
| Characteristic | Arm I (ADT, Abiraterone, Prednisone) | Arm II (ADT, Abiraterone, Prednisone, Radiation Therapy) | Total |
|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 6.1 | 64.3 years STANDARD_DEVIATION 12 | 63.0 years STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 2 / 6 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Percent Change in Peripheral Blood Effector T-cells (CCR7-/CD45RO)
Percent change in peripheral blood effector T-cells will be calculated by measuring the difference of the percent peripheral blood effector T-cells for each patient between two time points: pre-treatment and post-treatment (3 months after start of ADT, which is also 1 month post-radiation in the radiation arm). Unpaired two-sample t-test or Wilcoxon rank-sum test, depending on distribution of the percent change, will be used to test the null hypothesis that the percent change in peripheral blood effector T-cells is equal between the two arms.
Time frame: Baseline to 3 months after start of antiandrogen therapy (ADT)
Population: Clinical trial closed early due to poor accrual. Enrolled patient numbers are much lower than expected (10 out of 30 patients enrolled). There is no funding to run the assays to analyze the data since the trial failed to complete accrual. The original collaborators who were supposed to pay for the assays withdrew due to low patient numbers, and lack of ability to draw scientific conclusions from low patient numbers.
Secondary
Incidence of Adverse Events
Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety and tolerability as evaluated by the incidence, severity, duration, causality, seriousness of adverse events. Toxicities will be summarized as the number of patients with grade 3 or higher toxicities per CTCAE v4.0, in addition to total number of toxicities (allowing for multiple toxicities within a patient) among all patients, and per treatment arm.
Time frame: Up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (ADT, Abiraterone, Prednisone) | Incidence of Adverse Events | 2 Participants |
| Arm II (ADT, Abiraterone, Prednisone, Radiation Therapy) | Incidence of Adverse Events | 0 Participants |
Secondary
Rate of Undetectable Prostate Specific Antigen (PSA) (< 0.2)
The number of patients with undetectable PSA at 6-months will be summarized by each arm and all combined.
Time frame: At 6 months after start of abiraterone acetate
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (ADT, Abiraterone, Prednisone) | Rate of Undetectable Prostate Specific Antigen (PSA) (< 0.2) | 1 Participants |
| Arm II (ADT, Abiraterone, Prednisone, Radiation Therapy) | Rate of Undetectable Prostate Specific Antigen (PSA) (< 0.2) | 1 Participants |