Clinical Trials /

Apalutamide, Abiraterone Acetate, and Prednisone for the Treatment of Metastatic High Risk Castration Sensitive Prostate Cancer

NCT04267887

Description:

This phase II trial studies how well apalutamide, abiraterone acetate, and prednisone after chemotherapy work in treating patients with high risk prostate cancer that is sensitive to androgen deprivation therapy (castration sensitive) and has spread to other parts of the body (metastatic). 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. Antihormone therapy, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better in treating patients with castration sensitive prostate cancer.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Apalutamide, Abiraterone Acetate, and Prednisone for the Treatment of Metastatic High Risk Castration Sensitive Prostate Cancer
  • Official Title: Advanced ChemoHormonal Therapy for Treatment Naïve Metastatic Prostate Cancer: Apalutamide and Abiraterone Acetate With Prednisone and Androgen Deprivation Therapy After Treatment With Docetaxel and Androgen Deprivation Therapy

Clinical Trial IDs

  • ORG STUDY ID: STUDY00016728
  • SECONDARY ID: NCI-2020-00598
  • SECONDARY ID: STUDY00016728
  • SECONDARY ID: P30CA069533
  • NCT ID: NCT04267887

Conditions

  • Castration-Sensitive Prostate Carcinoma
  • Metastatic Prostate Carcinoma
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, Yonsa, ZytigaTreatment (apalutamide, abiraterone acetate, prednisone, ADT)
Antiandrogen TherapyADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation TherapyTreatment (apalutamide, abiraterone acetate, prednisone, ADT)
ApalutamideARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927Treatment (apalutamide, abiraterone acetate, prednisone, ADT)
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 (apalutamide, abiraterone acetate, prednisone, ADT)

Purpose

This phase II trial studies how well apalutamide, abiraterone acetate, and prednisone after chemotherapy work in treating patients with high risk prostate cancer that is sensitive to androgen deprivation therapy (castration sensitive) and has spread to other parts of the body (metastatic). 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. Antihormone therapy, such as abiraterone acetate, may lessen the amount of testosterone made by the body. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Apalutamide, abiraterone acetate, and prednisone after chemotherapy may work better in treating patients with castration sensitive prostate cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Efficacy of apalutamide in combination with abiraterone acetate + prednisone following
      docetaxel with ongoing androgen deprivation therapy in men with high risk metastatic
      castration sensitive disease.

      SECONDARY OBJECTIVES:

      I. Safety and tolerability of apalutamide in combination with abiraterone acetate +
      prednisone following docetaxel with ongoing androgen deprivation therapy.

      II. Time to event. III. Rate of conversion from AR-V7 negative to positive. IV. Depth of
      prostate specific antigen (PSA) response.

      EXPLORATORY OBJECTIVES:

      I. Quality of life. II. Falls.

      OUTLINE:

      Patients receive apalutamide orally (PO) once daily (QD), abiraterone acetate PO QD, and
      prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or
      unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of
      care.

      After completion of study treatment, patients are followed up every 6 months for up to 10
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (apalutamide, abiraterone acetate, prednisone, ADT)ExperimentalPatients receive apalutamide PO QD, abiraterone acetate PO QD, and prednisone PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive androgen deprivation therapy per standard of care.
  • Abiraterone Acetate
  • Antiandrogen Therapy
  • Apalutamide
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed prostate cancer OR a
             strong suspicion of prostate cancer as evidenced by metastatic disease in a pattern
             consistent with prostate cancer (such as blastic lesions on a nuclear medicine bone
             scan or lymphadenopathy on the computed tomography [CT] scan) AND a PSA > 50 ng/mL

          -  High risk disease (defined as meeting 2 of the 3: (1) visceral metastatic disease, (2)
             3 or more bone lesions, (3) Gleason 8-10)

          -  Use of androgen deprivation therapy (ADT) for neoadjuvant or adjuvant therapy is
             permitted, but at least 24 months MUST have elapsed since its use to day 1 of
             restarting ADT for metastatic castration sensitive disease

          -  ADT sensitive disease- no evidence of rising PSA or new metastatic deposits since
             starting ADT

          -  Have completed up to 6 cycles of docetaxel since developing metastatic castration
             sensitive disease with no more than 12 weeks elapsed since day 21 of the final cycle

          -  All races and ethnic groups will be included

          -  Life expectancy of greater than 18 months

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

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

          -  Leukocytes > 3,000/uL

          -  Absolute neutrophil count > 1,500/uL

          -  Platelets >= 100,000 x 10^9/uL, independent of transfusion and/or growth factors
             within 3 months prior to randomization

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (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)

          -  Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) <
             2.5 x institutional upper limit of normal

          -  Albumin > 3 g/dL

          -  Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m^2; per Modification of
             Diet in Renal Disease (MDRD) calculation or institutional standard

          -  Serum potassium >= 3.5 mmol/L

          -  Medications known to lower the seizure threshold must be discontinued or substituted
             at least 4 weeks prior to day 1 of study

          -  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

          -  Ability to understand, and the willingness to sign, a written informed consent
             document, as well as comply with study requirements.

        Exclusion Criteria:

          -  Subjects who are unwilling to stop taking saw palmetto, PC-SPECs or other herbal
             agents known to affect the PSA

          -  Patients may not have received any other investigational agents within 30 days prior
             to day 1 of study

          -  Prior exposure to apalutamide, enzalutamide, abiraterone acetate, darolutamide, or any
             other second-generation androgen receptor antagonist

               -  Note: prior exposure to bicalutamide, flutamide, nilutamide, or any other
                  first-generation androgen receptor antagonist is permitted. No washout is
                  required. Subjects may be on one of these at the time of consent, but it must be
                  stopped prior to day 1 of study treatment. These drugs are frequently used in the
                  newly diagnosed metastatic setting to blunt the effect of the testosterone spike

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to apalutamide or other agents used in the study

          -  Conditions that would interfere with treatment with docetaxel chemotherapy in the
             opinion of the treating physician (e.g. significant neuropathy)

          -  Subject has another active malignancy other than non-melanomatous skin cancer (unless
             it is metastatic) or superficial bladder cancer

          -  Either of the following:

               -  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)

               -  Severe or unstable angina, myocardial infarction, symptomatic congestive heart
                  failure or left ventricular ejection fraction < 50%, arterial or venous
                  thromboembolic events (e.g. pulmonary embolism, cerebrovascular accident
                  including transient ischemic attacks), or clinically significant ventricular
                  arrhythmias within 6 months prior to day 1 of study

          -  Current evidence of any of the following:

               -  Uncontrolled hypertension

               -  Gastrointestinal disorder affecting absorption

               -  Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis)

               -  Any chronic medical condition requiring a higher dose of corticosteroid than a
                  total of 10 mg prednisone/prednisolone daily

               -  Any condition that in the opinion of the investigator, would preclude
                  participation in this study.

               -  Avoid concomitant strong CYP3A4 inducers during abiraterone acetate treatment. If
                  a strong CYP3A4 inducer must be co-administered, increase the abiraterone acetate
                  dosing frequency to twice a day only during the co-administration period (e.g.,
                  from 1,000 mg once daily to 1,000 mg twice a day).

               -  Avoid co-administration of abiraterone acetate with CYP2D6 substrates that have a
                  narrow therapeutic index. If an alternative treatment cannot be used, exercise
                  caution and consider a dose reduction of the concomitant CYP2D6 substrate

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

          -  Inability to stop a prohibited medication:

               -  Atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone)

               -  Bupropion

               -  Lithium

               -  Meperidine and pethidine

               -  Phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine)

               -  Tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine,
                  maprotiline, mirtazapine

               -  Tramadol
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete prostate specific antigen (PSA) response
Time Frame:At 12 months from the start of treatment
Safety Issue:
Description:The complete PSA response is defined as a PSA =< 0.2 ng/ml, confirmed with a 2nd measurement at least 3 weeks later. The estimated PSA response rate will be computed with 95% exact confidence interval. Binomial exact test will be used to determine whether the complete PSA response rate is significantly greater than 43%.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:From day 1 of treatment, assessed up to 10 years
Safety Issue:
Description:
Measure:Incidence of adverse events >= grade 2
Time Frame:Up to 10 years
Safety Issue:
Description:Determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measure:Proportion of patients with PSA response >= 50% decrease
Time Frame:From baseline, assessed up to 12 months
Safety Issue:
Description:The proportion will be reported with 95% confidence interval.
Measure:Proportion of patients with PSA response >= 90% decrease
Time Frame:From baseline, assessed up to 12 months
Safety Issue:
Description:The proportion will be reported with 95% confidence interval.
Measure:Time to treatment failure
Time Frame:From start of treatment, assessed up to 10 years
Safety Issue:
Description:Kaplan-Meier plot will be used to describe the survival distributions.
Measure:Time to biochemical (PSA) progression
Time Frame:From start of treatment, assessed up to 10 years
Safety Issue:
Description:Kaplan-Meier plot will be used to describe the survival distributions.
Measure:Time to radiographic progression
Time Frame:From start of treatment, assessed up to 10 years
Safety Issue:
Description:Kaplan-Meier plot will be used to describe the survival distributions.
Measure:Time to symptomatic progressive disease
Time Frame:From start of treatment, assessed up to 10 years
Safety Issue:
Description:Kaplan-Meier plot will be used to describe the survival distributions.
Measure:Time to next therapy for metastatic castration resistant prostate cancer
Time Frame:From start of treatment, assessed up to 10 years
Safety Issue:
Description:Kaplan-Meier plot will be used to describe the survival distributions.
Measure:Proportion of patients with AR-V7 presence
Time Frame:Baseline and end of treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:OHSU Knight Cancer Institute

Last Updated

February 11, 2020