Antiandrogen Therapy, Abiraterone Acetate, and Prednisone With or Without Neutron Radiation Therapy in Treating Patients With Prostate Cancer

Radiation Enhancement of Local and Systemic Anti-Prostate Cancer Immune Responses

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Metastatic Malignant Neoplasm in the Bone; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8; Prostate Small Cell Neuroendocrine Carcinoma; Castration-Sensitive Prostate Carcinoma
• Intervention / Treatment: Drug: Antiandrogen Therapy; Drug: Abiraterone Acetate; Drug: Prednisone; Radiation: Radiation Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Antiandrogen Therapy; Undergo ADT; Other Names: ADT; Androgen Deprivation Therapy; Anti-androgen Therapy; Anti-androgen Treatment; Antiandrogen Treatment; Hormone Deprivation Therapy; Hormone-Deprivation Therapy; Androgen Deprivation Therapy (ADT); Drug: Abiraterone Acetate; Undergo Abiraterone Acetate Treatment SOC; Other Names: Zytiga; Yonsa; 17-(3-Pyridyl)-5,16-androstadien-3beta-acetate; 154229-18-2; Drug: Prednisone; Undergo Prednisone Treatment SOC; Other Names: Delta 1-Cortisone; 10023
Experimental: 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.	Drug: Antiandrogen Therapy; Undergo ADT; Other Names: ADT; Androgen Deprivation Therapy; Anti-androgen Therapy; Anti-androgen Treatment; Antiandrogen Treatment; Hormone Deprivation Therapy; Hormone-Deprivation Therapy; Androgen Deprivation Therapy (ADT); Drug: Abiraterone Acetate; Undergo Abiraterone Acetate Treatment SOC; Other Names: Zytiga; Yonsa; 17-(3-Pyridyl)-5,16-androstadien-3beta-acetate; 154229-18-2; Drug: Prednisone; Undergo Prednisone Treatment SOC; Other Names: Delta 1-Cortisone; 10023; Radiation: Radiation Therapy; Undergo neutron radiation therapy; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; Radiotherapeutics; RT; radiotherapy; NOS; ENERGY TYPE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 3 months after start of antiandrogen therapy (ADT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 6 months after start of abiraterone acetate
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.	Up to 6 months

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jing Zeng, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2020
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): February 1, 2023

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 15, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Neoplasms; Prostatic Neoplasms; Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Estrogens; Micronutrients; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Vitamins; Steroid Synthesis Inhibitors; Antioxidants; Anabolic Agents; Prednisone; Hormones; Abiraterone Acetate; Cortisone; Ascorbic Acid; Androgens; Methyltestosterone; Estrogens, Conjugated (USP); Androgen Antagonists
• Other Study ID Numbers: RG1001784; P50CA097186 (U.S. NIH Grant/Contract); 9938 (Other Identifier: CTEP); NCI-2018-01548 (Registry Identifier: NCI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No