Study of Abiraterone Acetate Plus ADT Versus APALUTAMIDE Versus Abiraterone and APALUTAMIDE in Patients With Advanced Prostate Cancer With Non-castrate Testosterone Levels

July 5, 2021 updated by: Latin American Cooperative Oncology Group

Phase II Randomized Study of Abiraterone Acetate Plus ADT Versus APALUTAMIDE Versus Abiraterone and APALUTAMIDE in Patients With Advanced Prostate Cancer With Non-castrate Testosterone Levels

Evaluation of the activity, safety and patients reported outcome of ADT plus abiraterone, abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or APALUTAMIDE alone in hormone naïve locally advanced or metastatic prostate cancer which ADT was indicated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Based on the current guidelines, ADT alone or combined with is antiandrogens are considered the appropriate active therapy for the patient population planned for this study. Recent data showed that chemotherapy also benefit patients in this setting. Even though, there is a clear unmet medical need for alternative treatment option in metastatic hormone sensitive prostate cancer (mHSPC). Treatments that can delay disease progression, and are associated with less comorbidities would be of significant clinical benefit in this patient population. The study is designed to assess the efficacy and safety of abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or APALUTAMIDE alone without castration side effects and the other arm a combination of ADT and abiraterone; this last arm is to reflect an Abiraterone ongoing pivotal trial (LATITUDE), that assess the efficacy of adding abiraterone to castration in this setting of patients. Abiraterone had already showed clinical benefit in CRPC patients without prior chemotherapy.

Study Type

Interventional

Enrollment (Actual)

128

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Rio de Janeiro, Brazil
        • Grupo COI
      • São Paulo, Brazil
        • Beneficiencia Portuguesa de São Paulo/Hospital São José
      • São Paulo, Brazil
        • Hospital Israelita Albert Einstein
      • São Paulo, Brazil
        • IBCC
      • São Paulo, Brazil
        • ICESP
    • Bahia
      • Salvador, Bahia, Brazil
        • Clinica AMO
    • Ceará
      • Fortaleza, Ceará, Brazil
        • CRIO
    • Paraná
      • Curitiba, Paraná, Brazil
        • Hospital Erasto Gaertner
    • RJ
      • Rio de Janeiro, RJ, Brazil, 22281 100
        • Oncologia Rede D'Or S.A.
    • Rio Grande Do Norte
      • Natal, Rio Grande Do Norte, Brazil
        • Liga Norte Riograndense de Oncologia
    • Rio Grande Do Sul
      • Ijuí, Rio Grande Do Sul, Brazil
        • Hospital de Caridade de Ijui
      • Porto Alegre, Rio Grande Do Sul, Brazil
        • CPO - Pucrs
    • São Paulo
      • Barretos, São Paulo, Brazil
        • Hospital de Cancer de Barretos
      • Santo André, São Paulo, Brazil
        • Centro de Pesquisa Clínica em Hematologia e Oncologia - CEPHO

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Histologically confirmed prostate adenocarcinoma;

  2. Hormone naïve patients with indication to ADT in the following settings:

    • Advanced loco-regional disease not amenable to curative local therapy (surgery or radiotherapy): T category T3/4 or node positive
    • Biochemical relapse after primary treatment (surgery or radiotherapy): patients in whom primary therapy is not appropriate or feasible with Previously treated with radical surgery and/or radiotherapy, now relapsing with at least one of the criteria: PSA >= 4 ng/ml and rising with doubling time less than 10 months. or PSA >= 20 ng/ml or N+ or M+
    • Newly diagnosed metastatic disease: Tany Nany M+
  3. Patient is asymptomatic or moderately symptomatic regarding bone symptoms, i.e., no need for palliative radiation or radionuclide therapy;
  4. Non-castration level of testosterone > 230ng/dL (> 8 nmol/L);
  5. Baseline level of prostatespecific antigen (PSA) > 2ng/dL;
  6. ECOG performance status of 0 to 2;

  7. Adequate hematologic, hepatic and renal function:

    1. hemoglobin > 10 g/dL, neutrophils > 1.5×109 / L, platelets> 100×109 / L;
    2. total bilirubin < 1.5x upper limit of normal (ULN); alanine (ALT) and aspartate (AST) aminotransferase < 2.5 x ULN;
    3. serum creatinine < 1.5x ULN; potassium > 3.5 mM;
  8. No previous cancer (except treated basal-cell skin cancer);
  9. Written informed consent obtained prior to any study procedure;
  10. Men age 18 years and older;
  11. Agrees to use a condom 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.

Exclusion Criteria:

  1. Prostate adenocarcinoma with neuroendocrine differentiation or small cell histology;
  2. Biochemical recurrence without evidence of clinical or radiological disease;
  3. Use of hormonal therapy or chemotherapy prior to randomization. Exception is courses of hormone therapy for localised disease must have been completed at least 12 months previously. It can have been given as adjuvant or neoadjuvant therapy.
  4. Prior radiation therapy for a primary tumour within the 3 months before enrollment or for the treatment of metastases;
  5. Known or suspected brain or skull metastases or leptomeningeal metastatic disease;
  6. Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study;
  7. Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study;
  8. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction;
  9. Current or prior treatment with anti-epileptic medications for the treatment of seizures;

  10. Impaired cardiac function, including any of the following:

    1. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic BP ≥95 mmHg);
    2. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease;
    3. Existing atrial fibrillation with or without pharmacotherapy. Other cardiac arrhythmia requiring pharmacotherapy;
    4. History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect);
  11. Specific underlying conditions for oral agents. For example: impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of abiraterone or APALUTAMIDE (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

  12. General excluded medications (e.g., relevant to cytochrome P450 interactions)

    1. Use of prescription drugs within 14 days prior to dosing or over-the-counter (OTC) medication within 7 days prior to dosing;
    2. Consumption of grapefruit product or St John's wort within 7 days prior to dosing;
    3. G-CSF, GM-CSF, erythropoietin, etc;
    4. Coumadin;
    5. Drugs which may cause QT prolongation;
    6. Known sensitivity to drugs or metabolites from similar classes;
    7. Known or suspected contraindications or hypersensitivity to APALUTAMIDE, bicalutamide or GnRH agonists or any of the components of the formulations;
  13. Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject's participation in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Abiraterone acetate + Prednisone + ADT (Goserelin)
  • Abiraterone administered at a single 1000 mg daily oral dose (4 x 250-mg tablets)
  • Prednisone administered at a 5 mg twice daily oral dose
  • Goserelin administered as subcutaneous injections of 10.8mg every 3 months
Drug: Apalutamide
APALUTAMIDE 240-mg orally once daily (4 x 60-mg tablets) will be administered on a continual basis. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days.
Drug: Abiraterone
Abiraterone acetate 1,000 mg (four 250 mg tablets) should be taken orally once daily, in combination with oral dose prednisone 5mg twice daily continuously. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days
Drug: ADT
Dosing of goserelin (dose and frequency of administration) will be consistent with the prescribing information and should only be adjusted if clinically indicated to achieve and maintain subcastrate concentrations of testosterone (50 ng/dL or 1.7 nM).
Other Names:
  • Goserelin
Experimental: APALUTAMIDE monotherapy
o APALUTAMIDE administered at a single 240 mg daily oral dose (4 x 60 mg tablets)
Drug: Apalutamide
APALUTAMIDE 240-mg orally once daily (4 x 60-mg tablets) will be administered on a continual basis. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days.
Experimental: Abiraterone acetate + Prednisone + APALUTAMIDE
  • Abiraterone administered at a single 1000 mg daily oral dose (4 x 250 mg tablets)
  • Prednisone administered at a 5 mg twice daily oral dose
  • APALUTAMIDE administered at a single 240 mg daily oral dose (4 x 60 mg tablets)
Drug: Apalutamide
APALUTAMIDE 240-mg orally once daily (4 x 60-mg tablets) will be administered on a continual basis. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days.
Drug: Abiraterone
Abiraterone acetate 1,000 mg (four 250 mg tablets) should be taken orally once daily, in combination with oral dose prednisone 5mg twice daily continuously. For the purpose of scheduling the study assessments and treatment compliance a treatment cycle is defined as 28 days
Drug: Prednisone
Subjects will receive prednisone 10mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients that achieves an undetectable PSA level, defined as ≤ 0.2 ng/mL
Time Frame: Week 25
Week 25

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA progression rate
Time Frame: Week 25
Determination of PSA progression rate among the three experimental arms
Week 25
Comparison of PSA progression rate
Time Frame: Week 25
Comparison of PSA progression rate among the three experimental arms
Week 25
PSA response of 50 and 80%
Time Frame: Week 25
Determination of PSA response of 50 and 80% among the three experimental arms
Week 25
Comparison of PSA response of 50 and 80%
Time Frame: Week 25
Comparison of PSA response of 50 and 80% among the three experimental arms
Week 25
Maximum PSA declines
Time Frame: Baseline up to week 25 to 52
Determination of maximum PSA declines among the three experimental arms
Baseline up to week 25 to 52
Overall PSA change
Time Frame: Baseline up to week 25 to 52
Determination of overall PSA change among the three experimental arms
Baseline up to week 25 to 52
Hormonal levels during treatment
Time Frame: Baseline up to week 25
Baseline up to week 25
Comparison of hormonal levels during treatment
Time Frame: Baseline up to week 25
Comparison of hormonal levels during treatment among the three experimental arms
Baseline up to week 25
Evaluation of bone mineral density according to RECIST 1.1
Time Frame: Week 25
Week 25
Comparison of bone mineral density according to RECIST 1.1 between three experimental groups
Time Frame: Week 25
Week 25
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: Baseline to 2 years of follow-up
Baseline to 2 years of follow-up
Number of participants with pain progression assessed by BPI-SF of three experimental arms
Time Frame: Baseline up to week 25
Baseline up to week 25
Number of participants in opioid use during treatment among three experimental arms
Time Frame: Baseline up to week 25
Baseline up to week 25
Comparison of pain progression assessed by opioid use
Time Frame: Baseline up to week 25
Comparison of pain progression assessed by opioid use between the experimental arms
Baseline up to week 25
Comparison of pain progression assessed by BPI-SF questionnaire
Time Frame: Baseline up to week 25
Comparison of pain progression assessed by BPI-SF between the experimental arms
Baseline up to week 25
Quality of life assessed by FACT-P questionnaire
Time Frame: Baseline up to week 25
Quality of life assessed by FACT-P questionnaire of the experimental arms
Baseline up to week 25
Comparison of quality of life assessed by FACT-P questionnaire
Time Frame: Baseline up to week 25
Comparison of quality of life assessed by FACT-P questionnaire between the experimental arms
Baseline up to week 25
Radiographic progression-free survival (rPFS)
Time Frame: Week 25
Radiographic progression-free survival (rPFS) among the experimental arms
Week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Latin American Cooperative Oncology Group

Collaborators

Janssen Pharmaceuticals

Investigators

  • Study Director: Gustavo Werutsky, MD, Latin American Cooperative Oncology Group
  • Principal Investigator: Fernando Maluf, MD, Beneficiência Portuguesa de São Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 11, 2017

Primary Completion (Actual)

October 9, 2019

Study Completion (Actual)

June 30, 2021

Study Registration Dates

First Submitted

August 8, 2016

First Submitted That Met QC Criteria

August 10, 2016

First Posted (Estimate)

August 15, 2016

Study Record Updates

Last Update Posted (Actual)

July 7, 2021

Last Update Submitted That Met QC Criteria

July 5, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LACOG 0415

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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