Clinical Trials /

A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

NCT03009981

Description:

This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
  • Official Title: A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: AFT-19
  • NCT ID: NCT03009981

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
ApalutamideArm B: Degarelix/Apalutamide
DegarelixFirmagonArm A: Degarelix Monotherapy
Abiraterone AcetateZytigaArm C: Degarelix/Apalutamide/Abiraterone/Prednisone
PrednisoneArm C: Degarelix/Apalutamide/Abiraterone/Prednisone

Purpose

This is a randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry.

Detailed Description

      Patients will be stratified by PSA doubling time (< 3 months vs. 3-9 months) and randomized
      in 1:1:1 fashion to one of three treatment arms: (1) Control arm consisting of degarelix
      monotherapy, (2) Experimental arm consisting of apalutamide in combination with degarelix,
      and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and
      degarelix. Patients will be treated for a maximum duration of 52 weeks and then enter follow
      up phase until the time of PSA progression, development of metastasis, or patient withdrawal
      from study, whichever occurs first. Patients with PSA progression will be followed long term
      until the development of castration resistance, first metastasis, and death.

      The primary endpoint of the study is PSA progression-free survival in the intent-to-treat
      patient population. PSA progression during the 52-week treatment period is defined as a
      rising PSA confirmed on repeat measurement, and at least 25% and 2 ng/mL above nadir or
      baseline, whichever is lower. PSA progression during follow up defined as PSA > 0.2 ng/mL
      confirmed by repeat measurement at least 2 weeks later. Secondary study endpoints include
      PSA progression-free survival in testosterone-evaluable population, 36-month PSA
      progression-free survival rate in both intent-to-treat and testosterone-evaluable
      populations, time to testosterone recovery, time to castration resistance, metastasis-free
      survival, quality of life, and safety. Each experimental arm will be compared against the
      control arm in pair-wise fashion. The study is not powered to detect differences in primary
      or secondary endpoints between the two experimental arms.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Degarelix MonotherapyActive ComparatorPatients randomized to Arm A will receive degarelix subcutaneous injections every 28 days (+/- 4 days). Patients will receive loading dose of 240 mg (two 120 mg injections) on cycle 1 day 1, followed by maintenance dose of 80 mg subcutaneous injection on day 1 of subsequent cycles.
  • Degarelix
Arm B: Degarelix/ApalutamideExperimentalPatients randomized to Arm B will receive degarelix as specified above. In addition, patients will be instructed to take apalutamide 240 mg (four 60 mg tablets) orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period.
  • Apalutamide
  • Degarelix
Arm C: Degarelix/Apalutamide/Abiraterone/PrednisoneExperimentalPatients randomized to Arm C will receive degarelix and apalutamide as specified above. Patients will be instructed to take abiraterone acetate 1000 mg (four 250 mg tablets) and prednisone 5mg orally once daily starting on cycle 1 day 1 and continuing throughout 52-week treatment period. Patients randomized to Arm C will also be instructed to take prednisone 5 mg tablet once daily starting on cycle 1 day 1 and continuing throughout the 52-week treatment period.
  • Apalutamide
  • Degarelix
  • Abiraterone Acetate
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed prostate adenocarcinoma

          -  Prior radical prostatectomy

          -  Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time
             of study entry. Calculation of PSA doubling time should include the use of all
             available PSA values obtained within past 12 months prior to randomization, with a
             minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to
             localized therapy will be excluded. PSA doubling time to be estimated using Memorial
             Sloan Kettering Cancer Center online calculator
             (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)

          -  Prior adjuvant or salvage radiation or not a candidate for radiation based upon
             clinical assessment of disease characteristics and patient co-morbidities.

          -  Screening PSA > 0.5 ng/mL

          -  No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and
             radionuclide whole body bone scan per the judgment of the investigator. Abdominal
             and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed.
             Lesions identified on other imaging modalities (e.g. PSMA or choline PET) that are
             not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal
             lesions on bone scan should be followed up with additional imaging as clinically
             indicated.

          -  Screening serum testosterone > 150 ng/dL

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1

          -  Age ≥ 18 years

          -  Medications known to lower the seizure threshold (see Appendix 1) must be
             discontinued or substituted at least 4 weeks prior to study entry.

          -  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.

          -  Adequate organ function as defined by the following laboratory values at screening:

               -  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 Gilbert's syndrome, if total
                  bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct
                  bilirubin is ≤1.5 × ULN, subject may be eligible)

               -  Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.

               -  Estimated GFR > 45 ml/min using Cockroft-Gault equation

               -  Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors
                  within 3 months prior to randomization

               -  Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3
                  months prior to randomization

               -  Serum albumin ≥ 3.0 g/dL

        Exclusion Criteria:

          -  Prior androgen deprivation therapy and/or first generation anti-androgen (e.g.
             bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer.
             Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage
             setting before, during, and/or following radiation or surgery is allowed provided
             last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior
             to date of randomization and total duration of prior therapy is ≤ 36 months.

          -  Prior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate,
             galeterone) or second generation androgen receptor antagonist including apalutamide
             or enzalutamide

          -  Prior chemotherapy for prostate cancer except if administered in neoadjuvant or
             adjuvant setting

          -  Use of 5-alpha reductase inhibitor within 42 days prior to randomization

          -  Use of investigational agent within 28 days prior to randomization

          -  Use of other prohibited medications within 7 days prior to cycle 1 day 1 on study
             (Arms B and C only) (see Appendix 1 for list of prohibited medications)

          -  Prior bilateral orchiectomy

          -  Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within
             1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or
             other benign CNS or meningeal disease which may require treatment with surgery or
             radiation therapy)

          -  Uncontrolled hypertension

          -  Gastrointestinal disorder affecting absorption or the ability to swallow tablets

          -  Baseline severe hepatic impairment (Child-Pugh Class B & C)

          -  Intercurrent illness that is not controlled such as active infection, psychiatric
             illness/social situations that would limit compliance with study requirements

          -  Any chronic medical condition requiring a higher dose of corticosteroid than
             equivalent of 5 mg prednisone/prednisolone once daily
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA progression-free survival
Time Frame:36 months
Safety Issue:
Description:Progression free survival

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance Foundation Trials, LLC.

Trial Keywords

  • PSA
  • Degarelix
  • Apalutamide
  • Abiraterone Acetate
  • Radical Prostatectomy

Last Updated

March 27, 2017