Clinical Trials /

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

NCT03419234

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abiraterone Acetate and Antiandrogen Therapy With or Without Cabazitaxel and Prednisone in Treating Patients With Metastatic, Castration-Resistant Prostate Cancer Previously Treated With Docetaxel
  • Official Title: Cabazitaxel With Abiraterone Versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial

Clinical Trial IDs

  • ORG STUDY ID: EA8153
  • SECONDARY ID: NCI-2017-00389
  • SECONDARY ID: EA8153
  • SECONDARY ID: EA8153
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT03419234

Conditions

  • 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

Interventions

DrugSynonymsArms
Abiraterone AcetateCB7630, ZytigaArm A (abiraterone acetate, prednisone, cabazitaxel)
Antiandrogen TherapyADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation TherapyArm A (abiraterone acetate, prednisone, cabazitaxel)
CabazitaxelJevtana, RPR-116258A, Taxoid XRP6258, XRP-6258Arm A (abiraterone acetate, prednisone, cabazitaxel)
Prednisone.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-PrednisoneArm A (abiraterone acetate, prednisone, cabazitaxel)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in
      patients with castration-resistant prostate cancer (CRPC) that have previously received
      docetaxel and androgen deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC)
      can improve progression-free survival (PFS) compared to abiraterone acetate alone.

      SECONDARY OBJECTIVES:

      I. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in
      patients with CRPC that have previously received docetaxel and ADT for HSPC can increase the
      percentage of change in prostate-specific antigen (PSA) from baseline to week 12 of treatment
      as well as the maximum decline in PSA that occurs at any point after treatment compared to
      abiraterone acetate alone.

      II. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in
      patients with CRPC that have previously received docetaxel for HSPC can prolong time to PSA
      progression compared to abiraterone acetate alone.

      III. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in
      patients with CRPC that have previously received docetaxel for HSPC can improve radiographic
      response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) compared to
      abiraterone acetate alone.

      IV. To assess whether the addition of 6 cycles of cabazitaxel to abiraterone acetate in
      patients with CRPC that have previously received docetaxel and ADT for HSPC can prolong the
      overall survival (OS) compared to abiraterone acetate alone.

      V. To assess safety and tolerability of the combination of 6 cycles of cabazitaxel and
      abiraterone acetate.

      TERTIARY OBJECTIVES:

      I. To examine whether patients with circulating tumor cells (CTCs) positive for AR-V7 at
      baseline have a longer radiographic or clinical PFS to the combination of cabazitaxel and
      abiraterone acetate vs. abiraterone acetate alone.

      II. To examine whether the addition of cabazitaxel to abiraterone acetate can change the
      AR-V7 status of patients who are positive at study entry.

      III. To examine whether the addition of cabazitaxel to abiraterone acetate has any impact on
      future development of AR-V7 positivity at the time of disease progression.

      IV. To assess if the changes in total tumor burden from baseline to week 12 as assessed with
      sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) will differ
      between two arms.

      V. To correlate total tumor burden at the baseline as assessed with NaF PET/CT with the PFS.

      VI. To correlate heterogeneity of response from baseline to week 12 as assessed with NaF
      PET/CT with the PFS.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM A: Patients receive abiraterone acetate orally (PO) once daily (QD) on days 1-21,
      prednisone PO twice daily (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 intravenously (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 luteinizing hormone-releasing hormone (LHRH) agonist or antagonist, or surgical
      castration with bilateral orchiectomy.

      ARM B: 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.

      After completion of study treatment, patients are followed up every 3 or 6 months and then
      annually for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (abiraterone acetate, prednisone, cabazitaxel)ExperimentalPatients 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.
  • Abiraterone Acetate
  • Antiandrogen Therapy
  • Cabazitaxel
  • Prednisone
Arm B (abiraterone acetate, prednisone)Active ComparatorPatients 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.
  • Abiraterone Acetate
  • Antiandrogen Therapy
  • Prednisone

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:From randomization to radiographic progression, symptomatic deterioration or death, whichever occurs first, assessed for up to 5 years
Safety Issue:
Description: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

Measure:Percent change in PSA in serum
Time Frame:Baseline to 12 weeks
Safety Issue:
Description:Will be compared between the two arms using Wilcoxon rank sum test.
Measure:Maximum decline in PSA while on treatment
Time Frame:Baseline up to 30 days from last treatment on study
Safety Issue:
Description:Will be compared between the two arms using Wilcoxon rank sum test.
Measure:Time to PSA progression
Time Frame:Time from randomization to PSA progression, assessed for up to 30 days from last treatment on study
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method. Stratified log rank test will be used to compare between the two arms.
Measure:Overall survival (OS)
Time Frame:Time from randomization to time of death or date last known alive, assessed for up to 5 years
Safety Issue:
Description: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.
Measure:Radiographic response (complete and partial response) assessed per Response Evaluation Criteria in Solid Tumors 1.1
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Will be evaluated for toxicity and the percent of patients with various toxicities will be tabulated.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ECOG-ACRIN Cancer Research Group

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