Clinical trial NCT02254785: Cabazitaxel vs Abiraterone or Enzalutamide in Patients With Poor Prognosis Metastatic Castration-resistant Prostate Cancer
Official title: A Phase II, Randomized, Multi-center Study of Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis-metastatic Castration-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Castration-Resistant Prostatic Cancer
Keywords: poor prognosis
castrate-resistant prostate cancer
cabazitaxel
abiraterone
enzalutamide
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Ozmosis Research Inc.
First posted: 2014-10-02
Enrollment: 120
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical benefit rate
timeFrame: 12 weeks or more
Secondary outcomes:
measure: Duration of treatment time to progression
timeFrame: 12 weeks until disease progression
measure: Progression Free Survival
timeFrame: 12 weeks until disease progression
measure: Overall Survival
timeFrame: 12 weeks until 2 years after last study visit
Other outcomes:
Locations:
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Cantre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Kelowna
country: Canada
facility: BCCA - Kelowna
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA- Vancouver Center
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Oshawa
country: Canada
facility: Durham Regional Cancer Centre (Lakeridge Health)
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Center
state: Saskatchewan
Study officials:
affiliation: British Columbia Cancer Agency
name: Kim N Chi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Annala M, Fu S, Bacon JVW, Sipola J, Iqbal N, Ferrario C, Ong M, Wadhwa D, Hotte SJ, Lo G, Tran B, Wood LA, Gingerich JR, North SA, Pezaro CJ, Ruether JD, Sridhar SS, Kallio HML, Khalaf DJ, Wong A, Beja K, Schonlau E, Taavitsainen S, Nykter M, Vandekerkhove G, Azad AA, Wyatt AW, Chi KN. Cabazitaxel versus abiraterone or enzalutamide in poor prognosis metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase II trial. Ann Oncol. 2021 Jul;32(7):896-905. doi: 10.1016/j.annonc.2021.03.205. Epub 2021 Apr 6.