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) (TAXYNERGY)

Sanofi

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer Metastatic

Treatments: Drug: CABAZITAXEL (XRP6258); Drug: Prednisone; Drug: DOCETAXEL (XRP6976)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01718353

CABAZL06056

U1111-1130-9893 (Other Identifier)

Details and patient eligibility

About

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).

Full description

• Participants were treated until progressive disease, unacceptable toxicity, death, or participant's refusal of further study treatment. All participants were followed until death or the study cut-off date, whichever came first.
• Study cut-off was 1 month after the last participant last treatment.
• Participants alive at the cut-off date were not followed for overall survival.

Enrollment: 63 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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63 participants in 2 patient groups

Docetaxel + Prednisone (Treatment A)

Experimental group

Description:

Docetaxel 75 mg/m\^2 intravenous (IV) infusion on Day 1 of Cycle 1 and every 3 weeks (q3w) thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Cabazitaxel 25mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until disease progression (DP), death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.

Treatment:

Drug: DOCETAXEL (XRP6976)

Drug: Prednisone

Cabazitaxel + Prednisone (Treatment B)

Experimental group

Description:

Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of Cycle 1 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily. Participants with \<30% PSA reduction from baseline at the end of Cycle 4 switched to Docetaxel 75mg/m\^2 IV infusion on Day 1 of Cycle 5 and q3w thereafter, in combination with Prednisone (or Prednisolone) 10 mg orally daily until DP, death, unacceptable toxicity or participant's refusal of further study treatment. Participants with ≥30% PSA reduction from baseline at the end of Cycle 4, continued on the same treatment which they received before switching until DP, death, unacceptable toxicity or participant's refusal of further study treatment.

Treatment:

Drug: Prednisone

Drug: CABAZITAXEL (XRP6258)