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EA8153: Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel (The CHAARTED2 Trial)

Description

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.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this trial is to determine progression-free survival.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
  • Had previous chemotherapy with at least three cycles of docetaxel for hormone-sensitive metastatic prostate cancer
  • Have 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)
  • Have the ability to swallow abiraterone acetate tablets as a whole
  • Are 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
  • Have castrate serum level of testosterone of < 50 ng/dL (< 1.73 nmol/L)
  • 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)
  • Have been or have not 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 four weeks (for flutamide) or six weeks (for bicalutamide or nilutamide) prior to registration and must have shown PSA progression after discontinuing the anti-androgen
  • Patients must have the following:
    • 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
  • 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
  • Had resected or irradiated brain metastases or had been 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, but agree to 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 includes:

  • The ability to lie still for imaging
  • Must weigh 300 pounds or less

Excluding patients who:

  • Had 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
  • Have a pure, small cell or other variant (non-adenocarcinoma) prostate cancer histology for which treatment with abiraterone would not be considered appropriate
  • Are not 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
  • Have a medical condition for which prednisone (corticosteroid) is contraindicated
  • Have an active infection requiring treatment with antibiotics
  • Have a history of adrenal insufficiency or hypoaldosteronism
  • Have 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
  • Had external beam radiation therapy within four weeks of registration
  • Have a history of allergic reactions to G-CSF
  • Have a history of allergic reactions to docetaxel and/or to medications formulated with polysorbate 80
  • Have a 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
  • Have a life expectancy of less than 12 months at screening
  • Have grade >= 2 neuropathy
  • Note: If total bilirubin is more than the upper limit of normal (ULN) (NOTE: in subjects with Gilbert’s syndrome, if total bilirubin is more than 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
     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)

Alan Tan

Theodore Pollock