Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Apalutamide With or Without Stereotactic Body Radiation Therapy in Treating Participants With Castration-Resistant Prostate Cancer (PILLAR) (PILLAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03503344
Recruitment Status : Recruiting
First Posted : April 19, 2018
Last Update Posted : June 4, 2020
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Rahul Aggarwal, University of California, San Francisco

Brief Summary:
This phase II trial studies the how well apalutamide with or without stereotactic body radiation therapy work in treating participants with castration-resistant prostate cancer. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. It is not yet known whether giving apalutamide with or without stereotactic body radiation therapy works better in treating participants with castration-resistant cancer.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma PSA Progression Stage IV Prostate Adenocarcinoma AJCC v7 Drug: Apalutamide Radiation: Stereotactic Body Radiation Therapy Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

I. To demonstrate whether the proportion of patients with an undetectable serum prostate specific antigen (PSA) at 6 months following cessation of apalutamide is higher with addition of stereotactic body radiation therapy (SBRT) to prostate specific membrane antigen (PSMA)-avid oligometastatic sites of disease compared to the group of patients receiving apalutamide monotherapy.

SECONDARY OBJECTIVES:

I. To compare the time to PSA progression by Prostate Cancer Working Group (PCWG) criteria between treatment arms.

II. To compare radiologic progression free survival (rPFS) between treatment arms.

III. To evaluate the safety and tolerability of apalutamide in combination with SBRT.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive apalutamide orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Beginning 60 days after first dose of apalutamide, participants also undergo stereotactic body radiation therapy for 1-5 fractions.

ARM II: Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed at for 30 days.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Study of Apalutamide +/- Stereotactic Body Radiotherapy (SBRT) in Castration-Resistant Prostate Cancer Patients With Oligometastatic Disease on PSMA-PET Imaging
Actual Study Start Date : December 17, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: Arm I (apalutamide, SBRT)
Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Beginning 60 days after first dose of apalutamide, participants also undergo stereotactic body radiation therapy for 1-5 fractions.
Drug: Apalutamide
Given PO, 240 mg per day (4 x 60mg tablets)
Other Names:
  • ARN 509
  • JNJ 56021927

Radiation: Stereotactic Body Radiation Therapy
Undergo SBRT
Other Names:
  • SABR
  • SBRT
  • Stereotactic Ablative Body Radiation Therapy

Active Comparator: Arm II (SBRT)
Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Apalutamide
Given PO, 240 mg per day (4 x 60mg tablets)
Other Names:
  • ARN 509
  • JNJ 56021927




Primary Outcome Measures :
  1. Proportion of patients with undetectable serum prostate specific antigen [ Time Frame: Approximately 18 months from date of randomization ]
    The primary endpoint for the study is the proportion of patients with undetectable serum PSA (< 0.2 ng/mL) at 6 months following completion of apalutamide therapy (18 months from date of randomization). Fisher's exact test will be used to compare the proportion in the two treatment arms. Patients who discontinue apalutamide prior to completion of 12 months of therapy for reasons other than disease progression by Prostate Cancer Clinical Trials Working Group (PCWG) criteria, as well as patients who withdraw or are lost to follow up, will be considered inevaluable for this analysis. Patients who discontinue treatment for radiographic or clinical progression, even if occurring prior to receipt of SBRT in the experimental arm), would be evaluable for analysis of the primary endpoint.


Secondary Outcome Measures :
  1. Time to PSA progression according to Prostate Cancer Working Group (PCWG) criteria [ Time Frame: Up to 36 months ]
    Comparison of time to PSA progression will be performed using a two-sided log-rank test. Kaplan-Meier methods will be used to estimate medians for each treatment arm. Cox proportional-hazard models, will be used to estimate the hazard ratio and its 95% confidence interval (CI).

  2. Radiologic progression free survival (rPFS) according to PCWG criteria [ Time Frame: Up to 36 months ]
    Comparison of time to radiographic progression-free survival will be performed using a two-sided log-rank test. Kaplan-Meier methods will be used to estimate medians for each treatment arm. Cox proportional-hazard models, will be used to estimate the hazard ratio and its 95% CI.

  3. Frequency of treatment-emergent adverse events (AEs) [ Time Frame: Up to 36 months ]
    Adverse events (AEs) will be classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. All AEs reported from the first dose of study drug until 30 days after the last dose of study drug will be considered as treatment-emergent AEs and will be summarized by treatment arm. For each treatment arm, all patients treated in that treatment arm will be included. Treatment-related AEs are those judged by the Investigator to be at least possibly related to the study treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Progressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with a minimum PSA > .05 ng/mL obtained during screening.

    • 5 lesions on conventional imaging with computed tomography (CT)/magnetic resonance imaging (MRI) of the abdomen/pelvis and whole body bone scan. A minimum of 50% of enrolled patients must have no definitive evidence of lesions on conventional imaging obtained during Screening
  • At least one but no more than 5 discrete PSMA-avid lesions on baseline PSMA-PET scan; all PSMA-avid lesions must be amenable to SBRT in judgment of treating radiation oncologist; there are no restrictions on site of lesions (e.g. bone, lymph node, visceral); equivocal lesions on PSMA PET scan that are not definitive for metastasis will not count towards the limit of lesions and will not undergo SBRT
  • Surgically or medically castrated, with testosterone levels of < 50 ng/dL during screening; if the patient is medically castrated, continuous dosing with luteinizing hormone-releasing hormone (LHRH) analogue must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone including post-treatment follow up period
  • No prior systemic treatment initiated for the treatment of castration resistant prostate cancer, including abiraterone acetate, enzalutamide, apalutamide, darolutamide, other novel AR or CYP17 antagonist, or docetaxel.
  • Patients receiving bone loss prevention treatment with bone-modifying agents (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization
  • Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
  • At least 4 weeks or 5 half-lives, whichever is shorter, must have elapsed from the use of any anti-cancer therapy, other than Luteinizing hormone-releasing hormone (LHRH) analog or first generation antiandrogen, prior to randomization
  • At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
  • Age > 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
  • Resolution of all acute toxic effects of prior therapy or surgical procedure to grade 1 or baseline prior to randomization
  • Serum aspartate transaminase (AST) ((serum glutamic oxaloacetic transaminase (SGOT])) and serum alanine transaminase (ALT) (( serum glutamic pyruvic transaminase (SGPT)) ≤ 2.5 x upper limit of normal (ULN)
  • Total serum bilirubin ≤ 1.5 x ULN; in subjects with known or suspected Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, direct bilirubin is ≤ 1.5 x ULN
  • Glomerular filtration rate ≥ 45 ml/min based on Cockcroft-Gault equation
  • Absolute neutrophil count (ANC) ≥ 1500/microliter
  • Platelets ≥ 75,000/microliter without transfusion and/or growth factors in the 3 months prior to randomization
  • Hemoglobin ≥ 9.0 g/dL without transfusion and/or growth factors in the 3 months prior to randomization
  • Serum albumin ≥ 3.0 g/dL
  • Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to randomization
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets and long-term follow-up
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

  • Presence of visceral lesions (e.g. lung, liver) detectable on cross-sectional imaging or bone lesions requiring the use of opioid analgesic or focal radiation treatment at the time of study entry
  • History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy
  • Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 1 week prior to randomization, except for medications known to lower seizure threshold which must be discontinued or substituted at least 4 weeks prior to randomization)
  • Medications known to lower the seizure threshold
  • Herbal (e.g., saw palmetto) and non-herbal (e.g., pomegranate) products that may decrease PSA levels
  • Systemic (oral/intravenous (IV)/intramuscular (IM)) corticosteroids; patients on chronic stable dose of steroids at an equivalent dose of prednisone ≤ 10 mg daily may be permitted to enroll at the discretion of principal investigator
  • Any other experimental treatment on another clinical trial
  • Any of the following within 6 months prior to randomization: Severe/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
  • Uncontrolled hypertension at study entry; patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by antihypertensive treatment
  • Gastrointestinal disorder affecting absorption
  • Secondary malignancy requiring active treatment except for non-melanoma skin cancer and superficial bladder cancer
  • Any medical condition that would be a contra-indication to radiation therapy, such as inflammatory bowel disease
  • Spinal cord compression or impending spinal cord compression
  • Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03503344


Contacts
Layout table for location contacts
Contact: Rahul R. Aggarwal, MD 877-827-3222 cancertrials@ucsf.edu
Contact: Kaleas Johnson (415) 502-5051 Kaleas.Johnson@ucsf.edu

Locations
Layout table for location information
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Rahul R. Aggarwal    877-827-3222    cancertrials@ucsf.edu   
Contact: Kaleas Johnson    (415) 502-5051    Kaleas.Johnson@ucsf.edu   
Principal Investigator: Rahul R. Aggarwal, MD         
Sponsors and Collaborators
University of California, San Francisco
Janssen Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Rahul Aggarwal, MD University of California, San Francisco
Layout table for additonal information
Responsible Party: Rahul Aggarwal, Associate Clinical Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03503344    
Other Study ID Numbers: 175519
NCI-2018-00572 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type