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

Sponsor

British Columbia Cancer Agency (Other)

Overall Status

Unknown status

CT.gov ID

NCT02254785

Collaborator

Sanofi (Industry), Ozmosis Research Inc. (Industry)

120

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-Resistant Prostatic Cancer	Drug: cabazitaxel Drug: Abiraterone Drug: Enzalutamide 160mg daily (oral)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Multi-center Study of Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis-metastatic Castration-resistant Prostate Cancer

Study Start Date :

Oct 1, 2014

Anticipated Primary Completion Date :

May 1, 2020

Anticipated Study Completion Date :

May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cabazitaxel	Drug: cabazitaxel Cabazitaxel 25mg/m2 intravenous every 3 weeks until disease progression Other Names: Jevtana
Active Comparator: Abiraterone or enzalutamide	Drug: Abiraterone Abiraterone 1000mg daily (oral) until disease progression Other Names: Zytiga Drug: Enzalutamide 160mg daily (oral) Enzalutamide 160mg daily (oral) until disease progression Other Names: Xtandi

Arm

Intervention/Treatment

Experimental: Cabazitaxel

Drug: cabazitaxel

Cabazitaxel 25mg/m2 intravenous every 3 weeks until disease progression

Other Names:

Jevtana

Active Comparator: Abiraterone or enzalutamide

Drug: Abiraterone

Abiraterone 1000mg daily (oral) until disease progression

Other Names:

Zytiga

Drug: Enzalutamide 160mg daily (oral)

Enzalutamide 160mg daily (oral) until disease progression

Other Names:

Xtandi

Outcome Measures

Primary Outcome Measures

Clinical benefit rate [12 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

Duration of treatment time to progression [12 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 Survival [12 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 Survival [12 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Box Hill Hospital	Box Hill	Victoria	Australia	3128
2	Monash Health-Monash Medical Centre	Clayton	Victoria	Australia	3168
3	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
4	Tom Baker Cancer Cantre	Calgary	Alberta	Canada	T2N 4N2
5	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
6	BCCA - Kelowna	Kelowna	British Columbia	Canada	V1Y 5J3
7	BCCA- Vancouver Center	Vancouver	British Columbia	Canada	V5Z 4E6
8	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
9	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
10	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
11	Durham Regional Cancer Centre (Lakeridge Health)	Oshawa	Ontario	Canada	L1G 2B9
12	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
13	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
14	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
15	Saskatoon Cancer Center	Saskatoon	Saskatchewan	Canada	27N 4H4