Clinical Trials /

Efficacy of Rotations Between Abiraterone Acetate and Apalutamide in mCRPC Patients

NCT03173859

Description:

A randomized phase II study comparing the sequential use of abiraterone followed after progression by apalutamide with alternating cycles of abiraterone and apalutamide

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy of Rotations Between Abiraterone Acetate and Apalutamide in mCRPC Patients
  • Official Title: A Randomized Phase II Study to Investigate the Efficacy of Rotations Between Abiraterone Acetate and Apalutamide Versus Sequential Administration in Chemo-naïve Metastatic Castration Resistant Prostate Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: 70/3/14073
  • SECONDARY ID: 2017-000443-41
  • NCT ID: NCT03173859

Conditions

  • Prostatic Neoplasms, Castration-Resistant

Interventions

DrugSynonymsArms
AbirateroneZytigaRotational
ApalutamideRotational

Purpose

A randomized phase II study comparing the sequential use of abiraterone followed after progression by apalutamide with alternating cycles of abiraterone and apalutamide

Detailed Description

      This is an open-label, randomized phase II study to investigate the feasibility of
      alternating cycles of treatment with abiraterone plus prednisone and apalutamide compared to
      sequential treatment of abiratereone plus prednisone followed by apalutamide. 7 centers in
      Greece will participate in the study.

      The study population consists of adult patients (over 18 years old) with histologically
      confirmed metastatic prostate adenocarcinoma who have disease progression - as defined by
      PCWG2 criteria - despite androgen deprivation therapy and who have not received prior therapy
      for their castration resistant disease.

      The purpose of the study is to determine the progression free survival, feasibility and
      safety profile of the experimental arm compared to standard of care.

      In the experimental arm alternating treatment will consist of repeating cycles of 24 weeks of
      treatment consisting of 12 weeks of abiraterone acetate 1000mg orally qd and prednisone 5mg
      orally bid, followed by 12 weeks of apalutamide 240 mg per day. There will be no wash out
      period between cycles.

      The comparative arm will be the standard regimen of abiraterone 1000mg orally qd plus
      prednisone 5mg orally bid until progression, followed thereafter by apalutamide 240mg orally
      qd until progression.
    

Trial Arms

NameTypeDescriptionInterventions
RotationalExperimentalAbiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 for 3 cycles, followed by apalutamide 240mg qD orally for 3 cycles. The duration of each cycle is 28 days
  • Abiraterone
  • Apalutamide
SequentialActive ComparatorAbiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 until disease progression, followed by apalutamide 240mg qD orally until second disease progression.
  • Abiraterone
  • Apalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Signed Informed Consent Age >18 years Histologically confirmed metastatic or advanced
             prostate cancer adenocarcinoma that has received no treatment for the castration
             resistant disease and has progressed during treatment with complete androgen blockade
             (luteinizing hormone releasing hormone agonist or antagonist and an antiandrogen eg.
             Bicalutamide).

        Availability of a representative formalin-fixed, paraffin-embedded tumor specimen (FFPE)
        that enabled definitive diagnosis of prostate cancer.

        Two rising PSA levels >2ng/ml measured 1 week apart during or following the most recent
        prior therapy for prostate cancer (PCWG2 criteria) or radiographic evidence of disease
        progression in bone with or without biochemical disease progression on the basis of the PSA
        value.

        Ongoing androgen deprivation, with serum testosterone <50ng/dl ECOG performance status 0-1
        at screening Adequate hematologic and organ function within 14 days before the first study
        treatment (hematologic parameters must be assessed >14 days after a prior transfusion, if
        any) as defined by

          -  Hemoglobin >9g/dl

          -  Neutrophils >1500/μL

          -  Platelet count >100000/μL

          -  Total bilirubin <1,5xULN with the following exception:

             o Patients with known Gilbert syndrome who have serum bilirubin<3xULN

          -  AST and ALT<2,5xULN with the following exception

             o Patients with bone-only metastasis may have AST<5xULN, provided that ALT <2,5xULN
             and total bilirubin <1,5xULN

          -  Serum albumin >3g/dl

          -  Serum potassium ≥3.5mmol/L

          -  Serum creatinine <1,5xULN or creatinine clearance of >50ml/min based on
             Cockcroft-Gault equation

          -  Agreement by patient and/or partner to use an effective form of contraception
             including surgical sterilization, reliable barrier method, birth control pills,
             contraceptive hormone implants or true abstinence and to continue its use for the
             duration of the study and for 6 months after the last dose of study treatment.

        Exclusion Criteria:

          -  Small cell or neuroendocrine prostate carcinoma Inability or unwillingness to swallow
             pills Malabsorption syndrome or other condition that would interfere with enteral
             absorption Congenital long QT syndrome or QTc>480msec NYHA Class II to IV heart
             failure or LVEF <50% or ventricular arrhythmia requiring medication Previous therapy
             for prostate cancer with CYP17 inhibitors including ketoconazole or investigational
             agents (VMT-VT-464, Orteronel etc) or novel antiandrogens (enzalutamide of OMD-208)
             for more than 7 days Presence of visceral metastasis History of another invasive
             cancer within 3 years from screening, with the exception of fully treated cancers with
             a remote probability of recurrence Duration of previous Androgen Deprivation Therapy
             <12months Active infection requiring IV antibiotics

        Clinically significant cardiovascular disease including the following:

          -  unstable angina,

          -  myocardial infarction within 6 months from screening, or

          -  cerebrovascular accident within 6 months from screening Major surgical procedure
             within 4 weeks prior to initiation of study treatment Treatment with an
             investigational agent within 4 weeks prior to initiation of study treatment
             Unresolved, clinical significant toxicity from prior treatment Hypersensitivity
             reaction to the active pharmaceutical ingredient or any of the tablet components Any
             medical condition that restrain the patient to comply with study and follow-up
             procedures Inability to comply with study and follow up procedures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Radiographic progression-free survival
Time Frame:Estimated up to 24 months
Safety Issue:
Description:time until radiographic progression as assessed by PCWG2 criteria

Secondary Outcome Measures

Measure:Overall survival
Time Frame:estimated up to 36 months
Safety Issue:
Description:time until death or lost to follow up
Measure:Time to cytotoxic therapy initiation
Time Frame:Estimated up to 24 months
Safety Issue:
Description:time until the beginning of chemotherapy
Measure:Time until PSA progression
Time Frame:Estimated up to 24 months
Safety Issue:
Description:time until PSA progression as defined by PCWG2 criteria
Measure:Incidence, nature and severity of AEs
Time Frame:Estimated up to 24 months
Safety Issue:
Description:recording of all AE/SAEs

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Athens

Trial Keywords

  • prostate cancer, abiraterone, apalutamide

Last Updated

May 31, 2017