AASUR in High Risk Prostate Cancer

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Janssen Pharmaceuticals; Weill Medical College of Cornell University; University of Michigan
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

The purpose of this study is to determine whether anti-testosterone medications, when administered before, during, and after high-dose, precision radiation, will be effective in preventing the prostate cancer from returning.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: ARN-509; Drug: Abiraterone; Drug: Leuprolide; Radiation: stereotactic, ultra-fractionated radiotherapy	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	58 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	ARN-509+Abiraterone Acetate+Leuprolide With Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase II Study
Study Start Date :	May 2016
Estimated Primary Completion Date :	May 2019
Estimated Study Completion Date :	May 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: patients with prostate cancer; Eligible patients will receive a total of 6 months of leuprolide, abiraterone, and ARN-509 to begin three months prior to RT and continuing until approximately 3 months post-RT. Patients will be assessed every 4 weeks (±1 week) (a cycle = 28 days) throughout their treatment with the study drugs, and at least once during RT.	Drug: ARN-509; Other Names: apalutamide; JNJ-56021927; Drug: Abiraterone; Drug: Leuprolide; Radiation: stereotactic, ultra-fractionated radiotherapy

Outcome Measures

Primary Outcome Measures :

1. proportion of patients with biochemical failure [ Time Frame: 36 months ]
   Biochemical failure is defined as an increase in PSA by more than 2ng/mL above the nadir value. PSA rise equals or exceeds 2ng/mL will be the date of failure.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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
• KPS ≥ 70%
• IPSS (International Prostate Symptom Score) ≤ 20F
• Patient must be available for follow-up
• Laboratory test findings within 28 days of study registration :
• Adequate hepatic function:
• Bilirubin ≤ 1.5 times the upper institutional limits of normal (ULN). 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
• SGPT (ALT) and SGOT (AST) ≤ 2.5 x ULN
• Adequate renal function with creatinine <2.0 x the institutional ULN
• Adequate hematologic function:
• Absolute neutrophil counts ≥ 1500 cell/mm3
• Platelets ≥ 100,000 cells/mm3 (independent of blood transfusion and/or growth factors within 3 months prior to registration)
• Hemoglobin value ≥9 g/dL at the Screening Visit (independent of blood transfusion and/or growth factors within 3 months prior to registration)
• Albumin ≥ 3.0 g/dL
• Potassium ≥ 3.5 mmol/L
• Patients with pelvic and/or retroperitoneal lymph nodes < 1.5 cm in short axis are eligible as they are not considered to have definitive metastases
• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
• Males 18 years of age and above
• The effects of apalutamide, abiraterone, leuprolide and stereotactic, ultra-hypofractionated 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 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 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 LHRH Agonist/Antagonist Therapy for </= 1 month prior to registration are permitted to enroll with study 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 (see section 5.5.2 apalutamide for a list of prohibited medications)
• 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 ECG changes that interfere with QT interval interpretation (e.g., left bundle branch block, frequent premature ventricular contractions)
• Prolonged QTc >450ms 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
• Concurrent treatment with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital)

Contacts and Locations

Contacts

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Contact: Sean M McBride, MD, MPH	212-639-5717
Contact: Michael Zelefsky, MD	212-639-6802

Locations

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United States, Maryland
John Hopkins Medical Center	Recruiting
Baltimore, Maryland, United States, 21287
Contact: Curtiland Deville, MD 202-537-4787
United States, Michigan
University of Michigan Health System	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Daniel Spratt, MD 734-936-4300
United States, New Jersey
Memorial Sloan Kettering Monmouth	Recruiting
Middletown, New Jersey, United States, 07748
Contact: Sean M McBride, MD, MPH 212-639-5717
Memorial Sloan Kettering Bergen	Recruiting
Montvale, New Jersey, United States, 07645
Contact: Sean McBride, MD, MSCE 212-639-5717
United States, New York
Memorial Sloan Kettering Commack	Recruiting
Commack, New York, United States, 11725
Contact: Sean McBride, MD,MPH 212-639-5717
Memorial Sloan Kettering Westchester	Recruiting
Harrison, New York, United States, 10604
Contact: Sean McBride, MD, MPH 212-639-5717
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Sean M McBride, MD,MPH 212-639-5717
Contact: Michael Zelefsky,, MD
Principal Investigator: Sean M McBride, MD, MPH
Weill Cornell Medical Center	Recruiting
New York, New York, United States, 10065
Contact: Ana Molina, MD 646-962-2072
Principal Investigator: Ana Molina, MD
Memorial Sloan Kettering Rockville	Recruiting
Rockville Centre, New York, United States
Contact: Sean McBride, MD,MPH 212-639-5717
United States, Pennsylvania
Thomas Jefferson University Hospital	Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Robert Den, MD 215-955-6702
Principal Investigator: Robert Den, MD

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Janssen Pharmaceuticals

Weill Medical College of Cornell University

University of Michigan

Investigators

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Principal Investigator:	Sean M McBride, MD, MPH	Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

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Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT02772588 History of Changes
Other Study ID Numbers:	15-334; c15-164 ( Other Identifier: Prostate Cancer Clinical Trials Consortium, LLC (PCCTC) )
First Posted:	May 13, 2016
Last Update Posted:	December 19, 2018
Last Verified:	December 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:

ARN-509; Abiraterone; Leuprolide; Intensity-Modulated and Image-Guided Radiation Therapy	15-334; apalutamide,; JNJ-56021927

Additional relevant MeSH terms:

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Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases	Leuprolide; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents