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Abiraterone Acetate and Antiandrogen Therapy With or Without Cabazitaxel and Prednisone in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer Previously Treated With Docetaxel

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03419234
Recruitment Status : Recruiting
First Posted : February 1, 2018
Last Update Posted : October 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Study Description
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Brief Summary:
This randomized phase II trial studies how well abiraterone acetate and antiandrogen therapy, with or without cabazitaxel and prednisone, work in treating patients with castration-resistant prostate cancer previously treated with docetaxel that has spread to other parts of the body. Androgens can cause the growth of prostate cancer cells. Hormone therapy using abiraterone acetate and antiandrogen therapy may fight prostate cancer by lowering and/or blocking the use of androgens by the tumor cells. Drugs used in chemotherapy, such as cabazitaxel and 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. Giving abiraterone acetate and antiandrogen therapy with or without cabazitaxel and prednisone may help kill more tumor cells.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma in the Soft Tissue Prostate Carcinoma Metastatic in the Bone Stage IV Prostate Adenocarcinoma AJCC v7 Drug: Abiraterone Acetate Drug: Antiandrogen Therapy Drug: Cabazitaxel Other: Laboratory Biomarker Analysis Procedure: Orchiectomy Other: Pharmacological Study Drug: Prednisone Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cabazitaxel With Abiraterone Versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial
Actual Study Start Date : February 8, 2018
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A (abiraterone acetate, prednisone, cabazitaxel)
Patients receive abiraterone acetate PO QD on days 1-21, prednisone PO BID on days 1-21. Courses of abiraterone acetate and prednisone repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive cabazitaxel IV over 1 hour on day 1, and treatment with cabazitaxel repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
 Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Antiandrogen Therapy
Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist
Other Names:
  • ADT
  • Androgen Deprivation Therapy
  • Anti-androgen Therapy
  • Anti-androgen Treatment
  • Antiandrogen Treatment
  • Hormone Deprivation Therapy
  • Hormone-Deprivation Therapy

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

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Orchiectomy
Undergo standard of care surgical castration with bilateral orchiectomy
Other Names:
  • Castration
  • Male Castration
  • Male Gonadectomy
  • orchidectomy

Other: Pharmacological Study
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 B (abiraterone acetate, prednisone)
Patients receive abiraterone acetate and prednisone as in Arm A. Patients also receive standard of care antiandrogen therapy with either LHRH agonist or antagonist, or surgical castration with bilateral orchiectomy.
 Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga

Drug: Antiandrogen Therapy
Receive standard of care antiandrogen therapy with either LHRH agonist or antagonist
Other Names:
  • ADT
  • Androgen Deprivation Therapy
  • Anti-androgen Therapy
  • Anti-androgen Treatment
  • Antiandrogen Treatment
  • Hormone Deprivation Therapy
  • Hormone-Deprivation Therapy

Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Orchiectomy
Undergo standard of care surgical castration with bilateral orchiectomy
Other Names:
  • Castration
  • Male Castration
  • Male Gonadectomy
  • orchidectomy

Other: Pharmacological Study
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


Outcome Measures
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Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: From randomization to radiographic progression, symptomatic deterioration or death, whichever occurs first, assessed for up to 5 years ]
    Will be compared between the two arms. Patients who are alive without progression will be censored at the date of last disease assessment.


Secondary Outcome Measures :
  1. Percent change in PSA in serum [ Time Frame: Baseline to 12 weeks ]
    Will be compared between the two arms using Wilcoxon rank sum test.

  2. Maximum decline in PSA while on treatment [ Time Frame: Baseline up to 30 days from last treatment on study ]
    Will be compared between the two arms using Wilcoxon rank sum test.

  3. Time to PSA progression [ Time Frame: Time from randomization to PSA progression, assessed for up to 30 days from last treatment on study ]
    Will be estimated using the Kaplan-Meier method. Stratified log rank test will be used to compare between the two arms.

  4. Overall survival (OS) [ Time Frame: Time from randomization to time of death or date last known alive, assessed for up to 5 years ]
    Will be estimated for each arm using the Kaplan-Meier method and the stratified logrank test will be used to compare this endpoint across treatments.

  5. Radiographic response (complete and partial response) assessed per Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 5 years ]
    Fisher's exact test will be used to compare rates between the two arms. Patients with radiographic response unknown or unevaluable will be considered as non-responders in this analysis.

  6. Incidence of adverse events assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days from last treatment on study ]
    Will be evaluated for toxicity and the percent of patients with various toxicities will be tabulated.


Other Outcome Measures:
  1. Change in AR-V7 status in circulating tumor cells [ Time Frame: Baseline up to 5 years ]
    Fisher's exact test will be used to compare the proportion of patients who become AR-V7 negative at follow-up assessments between the two arms among patients who are AR-V7 positive at baseline. Cox regression will be used to evaluate the associations between baseline AR-V7 status and PFS as well as OS and its interaction with treatment.


Eligibility Criteria
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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:

  • Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
  • Previous chemotherapy with at least 3 cycles of docetaxel for hormone-sensitive metastatic prostate cancer
  • Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT/magnetic resonance imaging [MRI] of abdomen/pelvis, bone scintigraphy or NaF PET/CT)
  • Ability to swallow abiraterone acetate tablets as a whole
  • All patients must be receiving standard of care androgen deprivation treatment (surgical castration versus LHRH agonist or antagonist treatment); subjects receiving LHRH agonist or antagonist must continue treatment throughout the time on this study
  • Patients must have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L)

  • Patients must have progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for PSA, measurable disease or non-measurable (bone) disease during treatment with ADT:

    • PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value >= 2.0 ng/mL
    • Measurable disease (by RECIST 1.1): > 20% increase in the sum of the longest diameters of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be more that 15 mm to be assessed for change in size
    • Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan (or NaF PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI)
  • Patients may or may not have been treated previously with a nonsteroidal antiandrogen, such as flutamide, bicalutamide or nilutamide; for patients previously treated with an antiandrogen, they must be off treatment for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration and must have shown PSA progression after discontinuing the anti-androgen
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Hemoglobin (HgB) >= 9.0 gr/dL
  • Platelets >= 100,000/mm^3
  • Creatinine < 2.0 mg/dL
  • Patients must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding
  • Patients with resected or irradiated brain metastases or those treated with stereotactic radiation therapy are eligible to enroll, provided that they do not require treatment with steroids that exceeds 10 mg of prednisone daily or equivalent
  • Sexually active males must use an accepted and effective method of double barrier contraception or abstain from sexual intercourse for the duration of their participation in the study and for 26 weeks after the last dose of study drug
  • NaF PET/CT OPTIONAL SUB-STUDY ELIGIBILITY CRITERIA
  • Ability to lie still for imaging
  • Weight =< 300 lbs (pounds)

Exclusion Criteria:

  • Any prior chemotherapy or androgen receptor (AR)-directed therapy for CRPC, (e.g. docetaxel, cabazitaxel, mitoxantrone, abiraterone acetate, ketoconazole, or enzalutamide); previous treatment with radium-223 or sipuleucel-T is allowed
  • Pure small cell or other variant (non-adenocarcinoma) prostate cancer histology for which treatment with abiraterone would not be considered appropriate
  • Patients may not be receiving other therapeutic investigational agents or be receiving concurrent anticancer therapy other than standard androgen deprivation therapy; concurrent treatment with agents to prevent skeletal-related events (such as zoledronic acid or denosumab) will be allowed as long as it was initiated prior to study entry
  • Any medical condition for which prednisone (corticosteroid) is contraindicated

  • If total bilirubin is > upper limit of normal (ULN) (NOTE: in subjects with Gilbert?s syndrome, if total bilirubin is

    > ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) or

  • Alanine (ALT) or aspartate (AST) aminotransferase > 1.5 x ULN
  • Active infection requiring treatment with antibiotics
  • History of adrenal insufficiency or hypoaldosteronism
  • Myocardial infarction or arterial thrombotic event within 6 months, heart failure of New York Heart Association class II or higher, uncontrolled angina, severe uncontrolled ventricular arrhythmia
  • External beam radiation therapy within 4 weeks of registration
  • Prior history of allergic reactions to G-CSF
  • Prior history of allergic reactions to docetaxel and/or to medications formulated with polysorbate 80
  • History of active malignancy; patients with a history of cancer that has been adequately treated and are free of disease recurrence for 3 years or more are allowed to participate; patients with non-melanoma skin cancers or carcinoma in situ of the bladder that have been adequately excised are eligible to participate
  • Life expectancy of < 12 months at screening
  • Grade >= 2 neuropathy
Contacts and Locations
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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): NCT03419234


Locations
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Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Christos Kyriakopoulos ECOG-ACRIN Cancer Research Group
More Information
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Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT03419234    
Other Study ID Numbers: EA8153
NCI-2017-00389 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA8153 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA8153 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Adenocarcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Cortisone
Docetaxel
Abiraterone Acetate
 Hormones
Androgens
Androgen Antagonists
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Antineoplastic Agents, Hormonal
Steroid Synthesis Inhibitors
Enzyme Inhibitors