Clinical Trials /

Abiraterone Acetate, Prednisone, and Apalutamide in Treating Patients With Hormone-Naive Metastatic Prostate Cancer

NCT03821792

Description:

This phase II trial studies how well abiraterone acetate, prednisone, and apalutamide work in treating patients with hormone-naive prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate and apalutamide may lessen the amount of androgen made by the body.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abiraterone Acetate, Prednisone, and Apalutamide in Treating Patients With Hormone-Naive Metastatic Prostate Cancer
  • Official Title: A Phase 2 Course Determining Study for Men With Hormone-Naïve Metastatic Prostate Cancer (HNMPCa)

Clinical Trial IDs

  • ORG STUDY ID: 2018-0533
  • SECONDARY ID: NCI-2018-03599
  • SECONDARY ID: 2018-0533
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03821792

Conditions

  • Metastatic Prostate Carcinoma
  • Prostate Adenocarcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, Yonsa, ZytigaTreatment (abiraterone acetate, prednisone, apalutamide)
ApalutamideARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927Treatment (abiraterone acetate, prednisone, apalutamide)
Prednisone.delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-PrednisoneTreatment (abiraterone acetate, prednisone, apalutamide)

Purpose

This phase II trial studies how well abiraterone acetate, prednisone, and apalutamide work in treating patients with hormone-naive prostate cancer that has spread to other places in the body. Androgen can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate and apalutamide may lessen the amount of androgen made by the body.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Determine if a baseline molecular-pathologic androgen receptor response (AR-response)
      signature predicts efficacy to abiraterone plus apalutamide in patients with hormone-naive
      metastatic prostate cancer (HNMPCa).

      SECONDARY OBJECTIVES:

      I. Evaluate the efficacy of abiraterone acetate plus apalutamide in patients with HNMPCa.

      II. Evaluate the safety of abiraterone acetate plus apalutamide in patients with HNMPCa.

      III. Explore the relationship between molecular markers and clinical efficacy outcomes.

      OUTLINE:

      Patient receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and
      apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then for up to 6
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abiraterone acetate, prednisone, apalutamide)ExperimentalPatient receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Cycles repeat every 28 days for 1 year in the absence of disease progression or unacceptable toxicity.
  • Abiraterone Acetate
  • Apalutamide
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate

          -  At least 2 of the 3 following high-risk prognostic factors:

               -  Gleason score of >= 8

               -  Presence of 3 or more lesions on bone scan

               -  Presence of measurable visceral (excluding lymph node disease) metastasis on
                  computed tomography (CT) or magnetic resonance imaging (MRI) (Response Evaluation
                  Criteria in Solid Tumors [RECIST] 1.1)

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Hemoglobin >= 9.0 g/dL independent of transfusion and/or growth factors within 3
             months prior to enrollment

          -  Platelet count >= 100,000/uL independent of transfusion and/or growth factors within 3
             months prior to enrollment

          -  Serum albumin >= 3.0 g/dL

          -  Medications known to lower the seizure threshold must be discontinued or substituted
             at least 4 weeks prior to study entry

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Calculated creatinine clearance (Cockcroft-Gault equation) >= 45 mL/min

          -  Serum potassium >= 3.5 mEg/L

          -  Serum magnesium >= 1.6 mg/dL

          -  Serum bilirubin < 1.5 x institutional upper limit of normal (IULN) (except for
             patients with known Gilbert's disease if total bilirubin is > 1.5 x ULN, measure
             direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be
             eligible)

          -  Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x IULN
             for patients without liver metastases. (Note: In subjects with Gilbert's syndrome, if
             total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct
             bilirubin is =< 1.5 x ULN, subject may be eligible. For patients with liver metastases
             AST or ALT < 4 x IULN is allowed)

          -  Able to swallow study drugs whole as a tablet/capsule

          -  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

          -  Patients must agree to tissue collection for correlative studies at the specified time
             points

        Exclusion Criteria:

          -  Small cell prostate cancer

          -  Treatment within 28 days of cycle 1 day 1: Any prior pharmacotherapy, radiation
             therapy, or surgery for metastatic prostate cancer. The following exceptions are
             permitted:

               -  Up to 3 months of antiandrogen therapy (ADT) with LHRH agonists or antagonists or
                  orchiectomy with or without concurrent anti-androgens prior to cycle 1 day 1.
                  Anti-androgens (flutamide, bicalutamide or nilutamide) for subjects receiving an
                  LHRH agonist must be discontinued within 2 weeks of cycle 1 day 1, or subjects
                  may have one course of palliative radiation or surgical therapy to treat symptoms
                  resulting from metastatic disease (e.g., impending cord compression or
                  obstructive symptoms) if it was administered at least 28 days prior to cycle 1
                  day 1. All adverse events associated with these procedures must be resolved at
                  least to grade 1 by cycle 1 day 1, or

          -  Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg
             prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and topical
             steroids are acceptable, as is a short course (i.e. =< 1 day) of corticosteroids to
             prevent a reaction to the intravenous (IV) contrast used for CT scans

          -  Active infection (requiring oral or IV antibiotics or antiviral therapy) or other
             medical condition that would make prednisone/prednisolone (corticosteroid) use
             contraindicated. Known history of testing positive for human immunodeficiency virus
             (HIV) or known acquired immunodeficiency syndrome (AIDS)

          -  A malignancy (other than the one treated in this study) which required radiotherapy or
             systemic treatment within the past 5 years, or has a >= 30% probability of recurrence
             within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)

          -  Chronically uncontrolled hypertension, defined conventionally as consistent systolic
             pressures above 170 or diastolic pressures above 110 despite anti-hypertensive
             therapy. Note that this is NOT a criterion related to particular blood pressure (BP)
             results at the time of assessment for eligibility, nor does it apply to acute BP
             excursions that are related to iatrogenic causes, acute pain or other transient,
             reversible causes. (For example doctor's visit related stress i.e. "white coat
             syndrome")

          -  Prolonged corrected QT interval by Fridericia's formula (QTcF) interval on pre-entry
             electrocardiogram (>= 450 msec)

          -  Known active or symptomatic viral hepatitis or chronic liver disease

          -  Clinically significant heart disease as evidenced by myocardial infarction, or
             arterial thrombotic events in the past 6 months, severe or unstable angina, history of
             clinically significant ventricular arrhythmias (such as ventricular tachycardia,
             ventricular fibrillation, or Torsade de pointes), New York Heart Association class
             III-IV heart disease or cardiac ejection fraction measurement of < 40% at baseline

          -  Patients who have had a history of illness which put them at current risk for bowel
             perforation such as acute diverticulitis, intra-abdominal abscess, gastrointestinal
             (GI) obstruction and abdominal carcinomatosis

          -  Baseline moderate and severe hepatic impairment (Child Pugh class B & C)

          -  Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1
             year 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)

          -  Gastrointestinal disorder affecting absorption

          -  Untreated symptomatic spinal cord compression

          -  Any underlying medical or psychiatric condition, which in the opinion of the
             investigator, will make the administration of study drug hazardous or obscure the
             interpretation of adverse events
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time on treatment
Time Frame:Up to 6 months
Safety Issue:
Description:Calculated as the time from start of protocol treatment

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:Time from starting treatment until progression, assessed up to 6 months
Safety Issue:
Description:Median PFS and 95% confidence interval will be presented for all patients and by the androgen receptor molecular-pathologic responsiveness signature.
Measure:Incidence of adverse events
Time Frame:Up to 6 months
Safety Issue:
Description:Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Measure:Efficacy assessed
Time Frame:Up to 6 months
Safety Issue:
Description:prostate specific antigen, bone specific alkaline phosphatase, and urine n-telopeptides
Measure:Expression of candidate markers
Time Frame:Up to 6 months
Safety Issue:
Description:Candidate markers for different biologic domains by immunohistochemistry, mass spectrometry (for steroid metabolome) and genomic profiling. Markers will encompass bone remodeling (e.g. integrin signaling), steroid metabolome (e.g. glucocorticoid receptor) and tumor immunoprofile (e.g. PD-1, PDL-1).
Measure:Overall survival
Time Frame:up to 6 months
Safety Issue:
Description:Time from start of protocol treatment until death or last contact

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 13, 2019