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Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02703623
Recruitment Status : Recruiting
First Posted : March 9, 2016
Last Update Posted : May 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This randomized phase II trial studies the side effects and how well abiraterone acetate, prednisone, and apalutamide work with or without ipilimumab or cabazitaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Drugs, such as abiraterone acetate and apalutamide may lessen the amount of androgens made by the body. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as prednisone, cabazitaxel, and carboplatin 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. It is not yet known whether giving abiraterone acetate, prednisone, and apalutamide with or without ipilimumab or cabazitaxel and carboplatin may be a better way to treat patients with castration-resistant prostate cancer that has spread to other places in the body.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma PSA Progression Stage IV Prostate Adenocarcinoma AJCC v7 Drug: Abiraterone Acetate Drug: Apalutamide Drug: Cabazitaxel Drug: Carboplatin Biological: Ipilimumab Other: Laboratory Biomarker Analysis Drug: Prednisone Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 265 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer
Actual Study Start Date : May 18, 2016
Estimated Primary Completion Date : May 1, 2020
Estimated Study Completion Date : May 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 2A (abiraterone acetate, prednisone, apalutamide)
Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • JNJ 56021927
  • JNJ-56021927

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Prednisone
Given PO
Other Names:
  • .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
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisonum
  • Prednitone
  • Promifen
  • Servisone
  • SK-Prednisone

Experimental: Arm 2B (abiraterone acetate, prednisone, ARN-509, ipilimumab)
Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab IV over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • JNJ 56021927
  • JNJ-56021927

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Prednisone
Given PO
Other Names:
  • .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
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisonum
  • Prednitone
  • Promifen
  • Servisone
  • SK-Prednisone

Active Comparator: Arm 3(abiraterone, prednisone, ARN509,cabazitaxel,carboplatin)
Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV, over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • JNJ 56021927
  • JNJ-56021927

Drug: Cabazitaxel
Given IV
Other Names:
  • Jevtana
  • RPR-116258A
  • Taxoid XRP6258
  • XRP-6258

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Prednisone
Given PO
Other Names:
  • .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
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisonum
  • Prednitone
  • Promifen
  • Servisone
  • SK-Prednisone




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 4 years ]
    Will be reported for each arm. Estimated by Bayesian posterior estimates along with the 95% credible intervals and presented using Kaplan-Meier curves.

  2. Incidence of adverse events as measured by the method of Thall et al [ Time Frame: Up to 4 years ]
    Will be reported overall as well as by grade and attribution to study drug for each arm.

  3. Androgen receptor (AR) response marker signature [ Time Frame: At baseline ]
    Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory).

  4. Allocation serum marker decline [ Time Frame: At 8 weeks ]
    Serum levels of prostate specific antigen (PSA) and circulating tumor cells (CTCs) will be evaluated and correlated with AR response marker signatures. Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory). Multivariate logistic regression analysis adjusting for the effects of other baseline factors will also be used to identify factors associated with a satisfactory allocation serum marker profile.


Secondary Outcome Measures :
  1. Time to treatment failure (TTF) [ Time Frame: Up to 4 years ]
    Estimated by Bayesian posterior estimates along with the 95% credible intervals and presented using Kaplan-Meier curves.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Willing and able to provide written informed consent
  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Presence of metastatic disease documented on imaging studies (bone scan, computed tomography [CT] and/or magnetic resonance imaging [MRI] scans)
  • Patients must have documented evidence of progressive disease as defined by any of the following:

    • Prostate-specific antigen (PSA) progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 1.0 ng/mL;
    • New or increasing non-bone disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1);
    • Positive bone scan with 2 or more new lesions (Prostate Cancer Clinical Trials Working Group [PCWG]3)
  • Surgically or ongoing medically castrated, with baseline testosterone levels of =< 50 ng/dL (=< 2.0 nM)
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Hemoglobin >= 7.5 g/dL in the presence of bone marrow involvement independent of transfusion and/or growth factors within 3 months prior to enrollment
  • Platelet count >= 100,000/uL independent of transfusion and or growth factors within 3 months prior to enrollment
  • Serum albumin >= 3.0 g/dL
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Calculated creatinine clearance (Cockcroft-Gault equation) >= 40 mL/min
  • Serum potassium >= institutional lower limit of normal (ILLN)
  • Serum magnesium >= ILLN
  • Serum bilirubin < 1.5 x institutional upper limit of normal (IULN) (except for patients with known Gilbert's disease)
  • Serum aspartate aminotransferases (AST) or alanine aminotransferases (ALT) < 2.5 x IULN for patients without liver metastases; for patients with liver metastases AST or ALT < 5 x IULN is allowed
  • Able to swallow study drugs whole as a tablet/capsule
  • Male subject with a female partner of childbearing potential or pregnant must agree to use two acceptable methods of contraception and not to donate sperm from time of screening until 3 months after the last dose of study treatments
  • Patients must agree to tissue collection for correlative studies (including participation in PA13-0291 and PA13-0247 for MD Anderson participants) at the specified timepoints

Exclusion Criteria:

  • Any prior treatment with: ipilimumab
  • Treatment within 28 days of cycle1 day1: any other systemic therapy for prostate cancer (with the exception of luteinizing hormone-releasing hormone [LHRH] agonists and LHRH antagonists for testosterone suppression, and bisphosphonates and RANK-ligand inhibitors for bone metastases which are allowed); any other investigational product
  • Treatment within 12 months of cycle 1 day 1 with any Cyp17-lyase inhibitor, any 2nd generation AR antagonist (e.g. enzalutamide), cabazitaxel or carboplatin
  • Patients treated with any Cyp17-lyase inhibitor, any 2nd generation AR antagonist (e.g. enzalutamide), cabazitaxel or carboplatin whose disease progressed while on treatment or within 3 months of its discontinuation; patients who have received any of these treatments more than 12 months from study entry and whose disease did not progress while on treatment or within 3 months of its discontinuation are allowed on study
  • Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy; any number of chemotherapies to which the patient's disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment)
  • Flutamide (Eulexin) treatment within 4 weeks of cycle 1, day 1 and bicalutamide (Casodex) or nilutamide (Nilandron) within 6 weeks of cycle 1 day 1 (exceptions: if progression is documented prior to this time interval, or if patient is deemed by the treating physician to be highly unlikely to respond to AR inhibitor withdrawal (e.g. if PSA did not decline for 3 months in response to AR inhibitor given as a second line or later intervention, or if patient has symptoms attributable to disease progression) only a 3 day washout prior to cycle 1, day 1 will be required for any of them
  • Radiation therapy for treatment of the primary tumor within 6 weeks of cycle 1, day 1; patients who have received palliative radiation and recovered are eligible
  • Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily; use of inhaled, intranasal, intra-articular and topical steroids is acceptable, as is a short course (i.e. =< 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans
  • Active infection (requiring oral or IV antibiotics or antiviral therapy) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated; known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • A malignancy (other than the one treated in this study) which required radiotherapy or systemic treatment within the past 5 years, or has a >= 30% probability of recurrence within 24 months (except for non-melanoma skin cancer or Ta urothelial carcinomas)
  • Uncontrolled hypertension (systolic blood pressure [BP] >= 140 mmHg or diastolic BP >= 90 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
  • Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (>= 450 msec)
  • Known active or symptomatic viral hepatitis or chronic liver disease
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), New York Heart Association (NYHA) class III-IV heart disease or cardiac ejection fraction measurement of < 40% at baseline
  • Autoimmune disease: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic progressive sclerosis [scleroderma and variants], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis] or autoimmune neuropathies (such as Guillain-Barre syndrome) are excluded from this study; vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary
  • Patients who have had a history of illness which put them at current risk for bowel perforation such as acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis
  • History of seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke or, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  • Gastrointestinal disorder affecting absorption
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events
  • Untreated symptomatic spinal cord compressions
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

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): NCT02703623


Contacts
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Contact: Ana M. Aparicio, MD 713-792-2830 aaparicio@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ana Aparicio    713-792-2830      
Principal Investigator: Ana Aparicio         
MD Anderson in Katy Not yet recruiting
Houston, Texas, United States, 77094
Contact: Jennifer Wang       jwang19@mdanderson.org   
Principal Investigator: Jennifer Wang         
MD Anderson in Sugar Land Not yet recruiting
Sugar Land, Texas, United States, 77478
Contact: Jennifer Wang       jwang19@mdanderson.org   
Principal Investigator: Jennifer Wang         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Ana Aparicio M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02703623     History of Changes
Other Study ID Numbers: 2014-0386
NCI-2016-00670 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0386 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 9, 2016    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019

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

Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Carboplatin
Prednisone
Ipilimumab
Abiraterone Acetate
Cortisone
Antineoplastic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Immunological
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors