AASUR in High Risk Prostate Cancer

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02772588

Collaborator

Janssen Pharmaceuticals (Industry), Weill Medical College of Cornell University (Other), University of Michigan (Other)

Enrollment

Locations

Arm

Duration (Months)

5.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

N/A

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 1, 2016

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

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

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

proportion of patients with biochemical failure [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	John Hopkins Medical Center	Baltimore	Maryland	United States	21287
2	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
3	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
4	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
5	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
6	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Weill Cornell Medical Center	New York	New York	United States	10065
9	Memorial Sloan Kettering Rockville	Rockville Centre	New York	United States
10	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
11	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107