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Cabazitaxel vs Abiraterone or Enzalutamide in Patients With Poor Prognosis Metastatic Castration-resistant Prostate Cancer

Phase 2
Conditions
Metastatic Castration-Resistant Prostatic Cancer
Interventions
Registration Number
NCT02254785
Lead Sponsor
British Columbia Cancer Agency
Brief Summary

The purpose of this study is to assess and compare the clinical benefit rate in patients with metastatic castrate-resistant prostate cancer and poor prognostic factors treated with cabazitaxel or novel hormonal agents (abiraterone or enzalutamide) as initial therapy, to determine which treatment is most active in this population. Clinical benefit rate is defined as PSA or measurable radiological response of any duration or stable disease for \> or equal to 12 weeks, in the absence of other indicators of progression.

There is option to cross-over onto the other arm if the patient progresses.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
120
Inclusion Criteria
  • Histological diagnosis of prostate adenocarcinoma.
  • Able and willing to provide informed consent and to comply with the study procedures
  • Age ≥18
  • Evidence of metastatic disease on a chest, abdominal, or pelvic CT scan and/or bone scan within 6 weeks of registration
  • Castration resistant disease defined as evidence of radiological and/or PSA progression despite castrate levels of testosterone (serum testosterone < 50 ng/dL (1.7 nmol/L)). For PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2. (Prostate Cancer Working Group 2 (PCWG2) criteria)
  • Poor prognosis disease as defined by any of the following:

the presence of liver metastases OR development of castration-resistance within 12 months of orchiectomy or commencement of LHRH antagonist/agonist for metastatic disease OR the presence of 4 or more of the following factors:

  • LDH > ULN
  • ECOG Performance status (PS) 2
  • visceral metastatic disease
  • serum albumin less than or equal to 4 g/dL
  • ALP > ULN
  • or < 36 months from commencement of initial androgen deprivation therapy to study enrollment
  • ECOG PS 0-2.
  • Adequate end-organ function within 14 days of registration:

Haemoglobin ≥ 90 g/L Neutrophils ≥ 1.5 x 109 /L Platelets ≥ 100 x 109/L AST < 1.5 x ULN ALT < 1.5 x ULN Bilirubin ≤ 1.0 x ULN (exceptions for Gilbert's syndrome) Creatinine ≤ 1.5 x ULN

  • At least 21 days have passed since completing radiotherapy (exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field or limited-field radiotherapy to non-marrow bearing area such as an extremity or orbit) at the time of randomization.
  • At least 21 days have passed since receiving any investigational agent at the time of registration.
  • At least 21 days have passed since major surgery.
  • Neuropathy ≤ grade 1 at the time of registration.
  • Has recovered from all therapy-related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) at the time of registration.
  • Eligible for abiraterone acetate and/or enzalutamide as per standard of care practices.
Exclusion Criteria
  • Histologic evidence of small cell/neuroendocrine prostate cancer.
  • Other chemotherapy regimen beyond one prior course of docetaxel.
  • Previously received treatment with cabazitaxel.
  • Received any prior next-generation anti-androgen (e.g. enzalutamide, ARN-509) or CYP 17 inhibitors (e.g. abiraterone, TAK-700).
  • Other condition, illness, psychiatric condition, or laboratory abnormality that may increase the risk associated with administration of cabazitaxel, abiraterone or enzalutamide, study participation, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Abiraterone or enzalutamideEnzalutamide 160mg daily (oral)-
Cabazitaxelcabazitaxel-
Abiraterone or enzalutamideAbiraterone-
Primary Outcome Measures
NameTimeMethod
Clinical benefit rate12 weeks or more

To assess and compare the clinical benefit rate in patients with mCRPC and poor prognostic factors treated with cabazitaxel or novel hormonal agents (abiraterone or enzalutamide) as initial therapy, to determine which treatment is most active in this population. Clinical benefit rate is defined as PSA or measurable radiological response of any duration or stable disease for greater than or equal to 12 weeks, in the absence of other indicators of progression.

Secondary Outcome Measures
NameTimeMethod
Duration of treatment time to progression12 weeks until disease progression

To measure the treatment time before any type of progression (symptomatic, PSA, or radiological) between Arm A and Arm B

Progression Free Survival12 weeks until disease progression

To measure the progression-free survival of metastatic castration-resistant prostate cancer patients following treatment with cabazitaxel or abiraterone/enzalutamide as initial therapy.

Overall Survival12 weeks until 2 years after last study visit

To measure the overall survival of metastatic castration-resistant prostate cancer patients following treatment with cabazitaxel or abiraterone/enzalutamide as initial therapy.

Trial Locations

Locations (15)

BCCA - Kelowna

🇨🇦

Kelowna, British Columbia, Canada

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Durham Regional Cancer Centre (Lakeridge Health)

🇨🇦

Oshawa, Ontario, Canada

BCCA- Vancouver Center

🇨🇦

Vancouver, British Columbia, Canada

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Saskatoon Cancer Center

🇨🇦

Saskatoon, Saskatchewan, Canada

Juravinski Cancer Centre

🇨🇦

Hamilton, Ontario, Canada

The Ottawa Hospital Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

Monash Health-Monash Medical Centre

🇦🇺

Clayton, Victoria, Australia

Tom Baker Cancer Cantre

🇨🇦

Calgary, Alberta, Canada

Box Hill Hospital

🇦🇺

Box Hill, Victoria, Australia

QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

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