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Trial record 4 of 10 for:    abiraterone | Prostate Cancer | Brazil

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

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ClinicalTrials.gov Identifier: NCT02867020
Recruitment Status : Recruiting
First Posted : August 15, 2016
Last Update Posted : October 18, 2017
Sponsor:
Collaborator:
Janssen Pharmaceuticals
Information provided by (Responsible Party):
Latin American Cooperative Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Apalutamide Drug: Abiraterone Drug: ADT Drug: Prednisone Phase 2

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  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 11, 2017
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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 Name: 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.




Primary Outcome Measures :
  1. Number of patients that achieves an undetectable PSA level, defined as ≤ 0.2 ng/mL [ Time Frame: Week 25 ]

Secondary Outcome Measures :
  1. PSA progression rate [ Time Frame: Week 25 ]
    Determination of PSA progression rate among the three experimental arms

  2. Comparison of PSA progression rate [ Time Frame: Week 25 ]
    Comparison of PSA progression rate among the three experimental arms

  3. PSA response of 50 and 80% [ Time Frame: Week 25 ]
    Determination of PSA response of 50 and 80% among the three experimental arms

  4. 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

  5. Maximum PSA declines [ Time Frame: Baseline up to week 25 to 52 ]
    Determination of maximum PSA declines among the three experimental arms

  6. Overall PSA change [ Time Frame: Baseline up to week 25 to 52 ]
    Determination of overall PSA change among the three experimental arms

  7. Hormonal levels during treatment [ Time Frame: Baseline up to week 25 ]
  8. Comparison of hormonal levels during treatment [ Time Frame: Baseline up to week 25 ]
    Comparison of hormonal levels during treatment among the three experimental arms

  9. Evaluation of bone mineral density according to RECIST 1.1 [ Time Frame: Week 25 ]
  10. Comparison of bone mineral density according to RECIST 1.1 between three experimental groups [ Time Frame: Week 25 ]
  11. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Baseline to 2 years of follow-up ]
  12. Number of participants with pain progression assessed by BPI-SF of three experimental arms [ Time Frame: Baseline up to week 25 ]
  13. Number of participants in opioid use during treatment among three experimental arms [ Time Frame: Baseline up to week 25 ]
  14. 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

  15. 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

  16. 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

  17. 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

  18. Radiographic progression-free survival (rPFS) [ Time Frame: Week 25 ]
    Radiographic progression-free survival (rPFS) among the experimental arms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867020


Contacts
Contact: Laura Voelcker 55 51 3384 5334 laura.voelcker@lacog.org.br
Contact: Raíra Maschmann 55 51 3384 5334 raira.maschmann@lacog.org.br

Locations
Brazil
Clínica AMO Recruiting
Salvador, Bahia, Brazil
Contact: Bruno Setenta         
Principal Investigator: Vanessa Dybal, MD         
CRIO Recruiting
Fortaleza, Ceará, Brazil
Contact: Monica Gomes         
Principal Investigator: Eduardo Cronemberger, MD         
CPO - Pucrs Recruiting
Porto Alegre, Rio Grande do Sul, Brazil
Contact: Virginia Webber         
Principal Investigator: André Fay, MD         
Oncologia Rede D'Or S.A. Recruiting
Rio de Janeiro, RJ, Brazil, 22281 100
Contact: Leandro Camara         
Principal Investigator: Daniel Herchenhorn         
Hospital de Câncer de Barretos Not yet recruiting
Barretos, São Paulo, Brazil
Contact: Ana Camila Alfano         
Principal Investigator: Ricardo Zylberberg, MD         
Centro de Pesquisa Clínica em Hematologia e Oncologia - CEPHO Not yet recruiting
Santo André, São Paulo, Brazil
Contact: Andressa Tamashiro         
Principal Investigator: Daniel Cubero, MD         
Grupo COI Not yet recruiting
Rio de Janeiro, Brazil
Contact: Débora Victorino         
Principal Investigator: Fábio Peixoto, MD         
Beneficiencia Portuguesa de São Paulo/Hospital São José Not yet recruiting
São Paulo, Brazil
Contact: Patricia Molina         
Contact: Daniel Lang         
Principal Investigator: Fernando Maluf, MD         
Hospital Israelita Albert Einstein Not yet recruiting
São Paulo, Brazil
Contact: Roberta Possato         
Principal Investigator: Oren Smaletz, MD         
ICESP Not yet recruiting
São Paulo, Brazil
Contact: Bárbara Penna         
Principal Investigator: David Muniz, MD         
Sponsors and Collaborators
Latin American Cooperative Oncology Group
Janssen Pharmaceuticals
Investigators
Principal Investigator: Fernando Maluf, MD Beneficiência Portuguesa de São Paulo
Study Director: Gustavo Werutsky, MD Latin American Cooperative Oncology Group

Publications:
Rathkopf DE, Antonarakis ES, Shore ND, et al: ARN-509 in men with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 31:abstr 48, 2013
Efstathiou E, Titus MA, Wen S, et al: Enzalutamide (ENZA) in combination with abiraterone acetate (AA) in bone metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol 32:abstr 5000, 2014

Responsible Party: Latin American Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT02867020     History of Changes
Other Study ID Numbers: LACOG 0415
First Posted: August 15, 2016    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Latin American Cooperative Oncology Group:
apalutamide
abiraterone
prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Abiraterone Acetate
Genital Diseases, Male
Prednisone
Methyltestosterone
Goserelin
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgens
Anabolic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors