Clinical Trials /

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

NCT03503344

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Apalutamide With or Without Stereotactic Body Radiation Therapy in Treating Participants With Castration-Resistant Prostate Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 175519
  • SECONDARY ID: NCI-2018-00572
  • SECONDARY ID: 17-24181
  • SECONDARY ID: PILLAR
  • SECONDARY ID: 175519
  • NCT ID: NCT03503344

Conditions

  • Castration Levels of Testosterone
  • Castration-Resistant Prostate Carcinoma
  • PSA Progression
  • Stage IV Prostate Adenocarcinoma AJCC v7

Interventions

DrugSynonymsArms
ApalutamideARN 509, JNJ 56021927Arm I (apalutamide, SBRT)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (apalutamide, SBRT)ExperimentalParticipants 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.
  • Apalutamide
Arm II (SBRT)Active ComparatorParticipants 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.
  • Apalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate

          -  Prior radical prostatectomy

          -  Progressive, castration-resistant prostate cancer demonstrated during continuous
             antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with the
             last PSA > 2 ng/mL

               -  5 metastases on conventional imaging with computed tomography (CT)/magnetic
                  resonance imaging (MRI) of the abdomen/pelvis and whole body bone scan

          -  At least one but no more than 5 discrete PSMA-avid metastases 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 metastasis (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 metastases and will not undergo SBRT

          -  Surgically or medically castrated, with testosterone levels of < 50 ng/dL; 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 abiraterone acetate, enzalutamide or apalutamide or other novel AR or CYP17
             antagonist, or docetaxel for castration resistant prostate cancer; if used for hormone
             naïve disease, last dose was at least 12 months prior to randomization

          -  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 prior to randomization

          -  At least 4 weeks must have elapsed from major surgery or radiation therapy prior to
             randomization

          -  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 ≥ 100,000/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 metastases (e.g. lung, liver) detectable on cross-sectional
             imaging or bone metastases 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients with undetectable serum prostate specific antigen (PSA) (< 0.2 ng/mL)
Time Frame:At 6 months following completion of apalutamide therapy
Safety Issue:
Description:Fisher's exact test will be used to compare the proportion in the two treatment arms.

Secondary Outcome Measures

Measure:Time to PSA progression according to Prostate Cancer Working Group (PCWG) criteria
Time Frame:Up to 36 months
Safety Issue:
Description:Comparison of time to PSA progression and 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% confidence interval (CI).
Measure:Radiologic progression free survival (rPFS) according to PCWG criteria
Time Frame:Up to 36 months
Safety Issue:
Description:Comparison of time to PSA progression and 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.
Measure:Incidence of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
Time Frame:Up to 30 days after last dose
Safety Issue:
Description:Will be summarized by treatment arm with frequency.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, San Francisco

Last Updated

September 24, 2019