Apalutamide, Abiraterone Acetate, Prednisone, Leuprolide Acetate, and Stereotactic, Ultra-hypofractionated Radiation Therapy in Treating Patients with Very High Risk Prostate Cancer

Status: Active

Description

This phase II trial studies how well apalutamide, abiraterone acetate, prednisone, leuprolide acetate, and stereotactic, ultra-hypofractionated radiation therapy work in treating patients with very high risk prostate cancer. Hormone therapy using apalutamide, abiraterone acetate, prednisone, and leuprolide acetate may fight prostate cancer by lowering the amount of androgen the body makes and / or blocking the use of androgen by the tumor cells. Stereotactic, ultra-hypofractionated radiation therapy is a type of radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving apalutamide, abiraterone acetate, prednisone, and leuprolide acetate, and stereotactic, ultra-hypofractionated radiation therapy may work better in treating patients with prostate cancer.

Eligibility Criteria

Inclusion Criteria

  • Histological or cytologic evidence of adenocarcinoma of the prostate confirmed at local institution
  • At least one of the following: * Two or more high risk features OR ** Gleason score 8-10 ** PSA >= 20 ng/mL within two months prior to registration ** Clinical stage >= T3 disease, as determined by standard digital rectal examination (DRE) ** Radiographic stage >= T3 disease as determined by a >= 75% probability of extracapsular extension or seminal vesicle invasion per reading radiologist * Any Gleason 9 or 10 disease OR * > 4 cores of Gleason 8 disease
  • Karnofsky performance status (KPS) >= 70%
  • IPSS (International Prostate Symptom Score) =< 20
  • Patient must be available for follow-up
  • Bilirubin =< 1.5 times the upper institutional limits of normal (ULN) (within 28 days of study registration); patients with a history of Gilbert's syndrome may be enrolled if the total bilirubin is < 3 mg/dL with a predominance of indirect bilirubin; if the total bilirubin is > 1.5 x the institutional ULN, direct and indirect bilirubin will be measured and if direct bilirubin is =< 1.5 x the institutional ULN, the patient will be eligible to participate
  • Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x ULN (within 28 days of study registration)
  • Creatinine < 2.0 x the institutional ULN (within 28 days of study registration)
  • Absolute neutrophil counts >= 1500 cell/mm^3 (within 28 days of study registration)
  • Platelets >= 100,000 cells/mm^3 (independent of blood transfusion and/or growth factors within 3 months prior to registration) (within 28 days of study registration)
  • Hemoglobin value >= 9 g/dL at the screening visit (independent of blood transfusion and/or growth factors within 3 months prior to registration) (within 28 days of study registration)
  • Albumin >= 3.0 g/dL (within 28 days of study registration)
  • Potassium >= 3.5 mmol/L (within 28 days of study registration)
  • Patients with pelvic and/or retroperitoneal lymph nodes < 1.5 cm in short axis are eligible
  • Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information * NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
  • The effects of apalutamide, abiraterone, leuprolide and stereotactic, ultrahypofractionated radiation on the developing human fetus at the recommended therapeutic dose are unknown; men (including men with vasectomies) must agree to use adequate contraception (a condom and another effective method of birth control) prior to registration, for the duration of study participation, and for at least 3 months thereafter; men must also agree not to donate sperm for the duration of study participation, and for at least 3 months thereafter

Exclusion Criteria

  • Radiographic evidence of metastatic disease
  • Patients with one or more positive lymph nodes as determined by radiographic assessment of MRI or computed tomography (CT) * NOTE: lymph nodes noted on MRI or CT to be > 1.5 cm on the short axis will require review by the local reference radiologist per institutional Response Evaluation Criteria in Solid Tumors (RECIST) review practices; if the lymph nodes are considered suspicious on repeat review, they must be confirmed negative for study participation
  • Prior treatment for prostate cancer; this includes any prior surgery (including transurethral resection of the prostate [TURP]), prostate cancer treatment), chemotherapy, radiation, or anti-androgen therapy/androgen deprivation therapy with the following exception: patients who will have been on luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy for =< 1 month prior to registration are permitted to enroll with study principal investigator (PI) approval
  • Prior use of steroidal antiandrogens (megestrol acetate, cyproterone acetate), AR partial agonists, ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals within 3 months before registration
  • Prior use of non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide) within 1 month before registration
  • Prior treatment with medications known to lower the seizure threshold within 4 weeks of registration
  • History of another malignancy within the previous 3 years except for the following: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, adequately treated stage I or stage II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 3 years
  • Severe hepatic impairment (Child-Pugh class C)
  • Concurrent treatment with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital)
  • Major surgery within 4 weeks of registration
  • Presence of a pacemaker
  • Active infection or other medical condition that would make prednisone use contraindicated
  • A known hypersensitivity to abiraterone acetate, apalutamide, and prednisone and/or any of their excipients
  • Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration
  • Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  • Any electrocardiograph (ECG) changes that interfere with QT interval interpretation (e.g., left bundle branch block, frequent premature ventricular contractions)
  • Prolonged corrected QT interval (QTc) > 450 milliseconds (ms) at the screening visit
  • Uncontrolled diabetes, heart disease, hypertension
  • Gastrointestinal disorder that may affect absorption of study treatment
  • Active symptomatic viral hepatitis or chronic liver disease
  • History of pituitary or adrenal dysfunction
  • Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone corticosteroid) use contraindicated
  • Patients with Crohn's disease or ulcerative colitis
  • Patients that cannot tolerate MRI
  • Inability to have fiducial markers placed
  • Any condition that in the opinion of the investigator, would preclude participation in this study
  • Enrollment concurrently in another investigational drug study or within 4 weeks of registration

Locations & Contacts

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Curtiland Deville
Phone: 202-537-4787

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Daniel Eidelberg Spratt
Phone: 734-936-4300

New Jersey

Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Sean Matthew McBride
Phone: 212-639-5717
Email: McBrides@mskcc.org
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Sean Matthew McBride
Phone: 212-639-5717

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Sean Matthew McBride
Phone: 212-639-5717
Email: McBrides@mskcc.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Sean Matthew McBride
Phone: 212-639-5717
Email: McBrides@mskcc.org
NYP / Weill Cornell Medical Center
Status: Active
Contact: Ana Maria Luisa Molina
Phone: 646-962-2072
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Sean Matthew McBride
Phone: 646-422-4491
Email: McBrides@mskcc.org
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Sean Matthew McBride
Phone: 212-639-5717
Email: McBrides@mskcc.org

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Contact: Robert Benjamin Den
Phone: 215-955-6702

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the rate of biochemical failure by 36 months post treatment in high risk prostate cancer patients treated with leuprolide acetate (leuprolide), abiraterone acetate, and apalutamide in conjunction with stereotactic, ultra-hypofractionated radiotherapy.

SECONDARY OBJECTIVES:

I. To determine the rate of positive prostate biopsies at 24 months (required) after completion of anti-androgen therapy.

II. To determine the rate of undetectable prostate specific antigen (PSA) at 1, 2, and 3 years post-treatment for men with non-castrate testosterone, (where undetectable PSA is defined as =< 0.2 ng/ml).

III. To determine overall survival.

IV. To determine the cumulative incidence of distant metastases and prostate cancer-specific death.

V. Evaluate acute and late toxicities, defined as any grade 3 or greater toxicity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 scoring scale.

VI. Evaluate the effects of treatment on health related (HR)-quality of life (QOL) outcomes, comparing baseline to subsequent follow-up using the Expanded Prostate Cancer Index Composite (EPIC)-26.

VII. Correlate magnetic resonance imaging (MRI) with correlative and biopsy results.

VII. To evaluate the predictive and prognostic capacity of the following biological correlatives: Memorial Sloan Kettering (MSK)-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), circulating tumor cells (CTCs), circulating tumor deoxyribonucleic acid (DNA) (ctDNA).

OUTLINE:

Patients receive abiraterone acetate orally (PO) once daily (QD) and apalutamide PO QD on days 1-28. Patients also receive prednisone PO twice daily (BID) on days 1-28 with a taper beginning on day 28 of course 6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive leuprolide acetate intramuscularly (IM) on day 5 of course 1 and on day 1 of course 4, and stereotactic, ultra-hypofractionated radiation therapy beginning on day 5 of course 4 for a total of 5 treatments.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for the second year, and every 6 months for the third year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Sean Matthew McBride

Trial IDs

Primary ID 15-334
Secondary IDs NCI-2016-01304
Clinicaltrials.gov ID NCT02772588