Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Condition: Prostate Cancer Metastatic
MeSH terms: Prostatic Neoplasms
Intervention: DOCETAXEL (XRP6976); CABAZITAXEL (XRP6258); Prednisone
Intervention description: Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous; Pharmaceutical form: Concentrate and solvent for solution for infusion Route of administration: Intravenous; Pharmaceutical form: Tablet Route of administration: Oral
Intervention MeSH terms: Prednisone; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Docetaxel and cabazitaxel are cancer chemotherapy agents of the taxane drug class. The
      purpose of this study is to explore the benefit, for treatment of metastatic
      castration-resistant prostate cancer (mCRPC), of a regimen in which participants begin
      treatment with either of these two taxane drugs (docetaxel or cabazitaxel, in combination
      with prednisone) and are switched to the other taxane drug if prostate-specific antigen (PSA)
      value does not decrease ≥30% after 4 cycles. As defined in study protocol amendment 3,
      efficacy results are summarized for all participants combined, irrespective of which agent
      (docetaxel or cabazitaxel) was administered initially, rather than separately for the two
      groups based on taxane administered initially. One of the primary outcome measures is
      percentage of participants with a ≥50% sustained decrease from baseline in PSA at any time
      during the trial. By providing an opportunity for patients to switch taxane based on early
      PSA response, there may be a difference in result for this measure versus result in a study
      where it was not possible to switch. The other primary outcome measures are change from
      baseline in circulating tumor cells (CTCs) biomarkers percent androgen receptor nuclear
      localization (%ARNL) and microtubule bundling (MTB).
    

Eligibility criteria:

        Inclusion criteria :

          -  Histologically- or cytologically-confirmed prostate adenocarcinoma with documented
             distant metastases (M1 disease).

          -  Progressive disease while receiving hormonal therapy or after surgical castration.

          -  Effective castration (serum testosterone levels ≤50 ng/dL) by orchiectomy and/or
             luteinizing hormone releasing hormone agonists or antagonist with or without
             anti-androgens.

        Exclusion criteria:

          -  Prior chemotherapy for prostate cancer, except estramustine and adjuvant/neoadjuvant
             treatment completed >3 years ago. Prior treatment with sipuleucel-T immunotherapy was
             allowed at the condition participant did not receive prior chemotherapy.

          -  Less than 28 days elapsed from prior treatment with estramustine, radiotherapy or
             surgery to the time of random allocation.

          -  Prior beta isotope therapy, whole pelvic radiotherapy, or radiotherapy to >30% of bone
             marrow.

          -  Adverse events (excluding alopecia and those listed in the specific exclusion
             criteria) from any prior anticancer therapy of grade >1(National Cancer Institute
             Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03) at the time of
             random allocation.

          -  Less than 18 years of age.

          -  Eastern Cooperative Oncology Group (ECOG) performance status >2.

          -  History of brain metastases, uncontrolled spinal cord compression, or carcinomatous
             meningitis or new evidence of brain or leptomeningeal disease.

          -  Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial
             (pTis, pTa and pT1) bladder cancer were allowed, as well as any other cancer for which
             chemotherapy had been completed ≥3 years ago and from which the participant had been
             disease-free for ≥3 years.

          -  Participation in another clinical trial and any concurrent treatment with any
             investigational drug within 30 days prior to random allocation.

          -  Any of the following within 6 months prior to study enrollment: myocardial infarction,
             severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York
             Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient
             ischemic attack.

          -  Any of the following within 3 months prior to random allocation: treatment resistant
             peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory
             bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled
             thromboembolic event.

          -  Acquired immunodeficiency syndrome (AIDS)-related illnesses or known HIV disease
             requiring antiretroviral treatment.

          -  Any severe acute or chronic medical condition which could impair the ability of the
             participant to participate in to the study or interfere with interpretation of study
             results, or participant unable to comply with the study procedures.

          -  Concomitant treatment with biphosphonates or denosumab except if the dose had been
             stable for 4 weeks prior to enrollment.

          -  Absence of signed and dated Institutional Review Board (IRB)-approved participant
             informed consent prior to enrollment into the study.

          -  Participants with reproductive potential who did not agree to use an accepted and
             effective method of contraception during the study treatment period. The definition of
             "effective method of contraception" was based on the investigator's judgment.

          -  History of hypersensitivity to docetaxel or polysorbate 80.

          -  Inadequate organ and bone marrow function.

          -  Contraindications to the use of corticosteroid treatment.

          -  Symptomatic peripheral neuropathy grade >2 (NCI CTCAE v.4.03).

          -  Treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a
             two-week wash-out period was necessary for participants who were already on these
             treatments).

        The above information was not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.