To evaluate the incidence of grade * 3 neutropenia (measured at Day 7 and Day 14) and/or neutropenic complications (febrile neutropenia, neutropenic infection) with two schedules of cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Grade *3 neutropenia (measured at D7 and D14 of each cycle) and/or neutropenic
complications (febrile neutropenia, neutropenic infection or sepsis) during the
overall treatment period
Secondary outcome
The following parameters will be evaluated in each arm:
*Dose reductions and dose delays
*Radiological progression-free survival (rPFS)
*Time to PSA progression
*Time to first symptomatic Skeletal-Related Event (SRE) and incidence of SREs
*Time to opioid treatment (if relevant)
*Prostate-specific antigen (PSA) response rate
*Quality of Life (FACT-P)
*Objective response rate (ORR) in measurable lesions (RECIST criteria 1.1 *
Appendix G)
*Overall Survival (OS)
*Factors influencing survival (duration of response to first androgen
deprivation therapy (ADT), serum testosterone, cumulative dose of cabazitaxel,
neutrophils/lymphocytes ratio, Gleason score, geriatric assessment G8, grade *3
neutropenia).
*Time to onset of grade *3 neutropenia
*Grade *3 neutropenia duration ( from date of onset of grade * 3 until grade *
2)
*Analysis of grade *3 neutropenia and/or neutropenia by cycle
*Adverse events
Background summary
There is growing evidence that the older men have more aggressive prostate
carcinomas. If elderly patients with localized prostate carcinoma are more
likely to receive a curative treatment than their younger counterparts, the
trend is in inverse proportion for older patients with metastatic disease who
receive less frequently chemotherapy probably due to concerns about
tolerability.
At present, physicians are tempted to treat elderly metastatic
castration-resistant prostate cancer (mCRPC) patients with new androgen
receptor (AR)-targeted agents, such as abiraterone acetate or enzalutamide,
since they have proven to prolong overall survival (OS), are orally delivered,
and well tolerated. However, because prostate cancer is a heterogeneous
disease, all of the patients will not respond to AR-targeted agents. Indeed,
some of them present a primary resistance to these agents, and others will
develop an acquired resistance in course of time. Moreover, retrospective
studies, involving a small number of patients, suggest that once a patient has
progressed with an AR-targeted agent, he will poorly respond to another
AR-targeted agent. Finally, the place of first-line androgen deprivation
therapy (ADT) for advanced prostate cancer is now strongly challenged.
Systematic review and meta-analysis of randomized studies in hormone-sensitive
prostate cancer also confirms that ADT plus 6 cycles docetaxel significantly
prolongs survival in hormone-sensitive metastatic prostate cancer and this
regimen is now recommended as standard of care by ESMO guidelines
The purpose of this phase III international, Randomized, open-label, is to
compared cabazitaxel 25 mg/m2 on Day 1 of a 3-week cycle plus daily prednisone
versus cabazitaxel 16 mg/m2 on Day 1 and Day 15 of a 4-week cycle in mCRPC
patients aged * 65 years.
We would like to confirm the improved safety profile of cabazitaxel bi-weekly
regimen in this study comparing cabazitaxel 25mg/m2 every 3 weeks versus
cabazitaxel 16 mg/m2 every 2 weeks until disease progression or unacceptable
toxicity. G-CSF will be given systematically according to European Organization
for Research and Treatment of Cancer (EORTC) recommendations
Study objective
To evaluate the incidence of grade * 3 neutropenia (measured at Day 7 and Day
14) and/or neutropenic complications (febrile neutropenia, neutropenic
infection) with two schedules of cabazitaxel (bi-weekly versus tri-weekly) plus
prednisone in elderly men (* 65 years) with mCRPC previously treated with a
docetaxel-containing regimen.
Study design
Randomized, open-label, phase 3 trial comparing cabazitaxel 25mg/m2 every 3
weeks versus cabazitaxel 16mg/m2 every 2 weeks in mCRPC patients aged * 65
years.
Intervention
Not applicable
Study burden and risks
The risks associated with this study are:
adverse effects due to study drugs
risks related with the study procedures
Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou 20-30, rue Leblanc
PARIS 75015
FR
Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou 20-30, rue Leblanc
PARIS 75015
FR
Listed location countries
Age
Inclusion criteria
1. Patient aged * 65 years with mCRPC previously treated with docetaxel
2. Medical or surgical castration with castrate level of testosterone (< 50
ng/dl) based on the EAU definition of castrate level of testosterone
3. Progressive disease according to PCWG2 (Appendix H)
4. Histologically proven prostate carcinoma
5. Health status allowing use of chemotherapy: G8 > 14; or G8 score * 14 with
geriatric assessment concluding to reversible impairment allowing use of
chemotherapy
6. ECOG-PS 0, 1 or 2(ECOG-PS 2 should be related to prostate cancer)
7. Adequate hematologic, liver and renal functions:
a) Neutrophil count *1.5 109/L
b) Haemoglobin *10 g/ dL
c) Platelet count *100.109/L
d) Total bilirubin * 1 the upper limit of normal (ULN)
e) Transaminases * 1.5 ULN
f) Serum creatinine * 2.0 ULN
8. Ongoing LHRH therapy at study entry
9. Signed informed consent
Exclusion criteria
1.History of severe hypersensitivity reaction (.grade 3) to docetaxel
2.History of severe hypersensitivity reaction (.grade 3) to polysorbate 80
containing drugs
3.Uncontrolled severe illness or medical condition (including uncontrolled
diabetes mellitus)
4.Concurrent or planned treatment with strong inhibitors or strong inducers of
cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who
are already on these treatments) (see Appendix E)
5.ECOG-PS >2 not related to prostate cancer disease
6.G8 . 14 with geriatric assessment contra-indicating standard cabazitaxel
regimen
7.Concomitant vaccination with yellow fever vaccine
8.Patient who cannot be regularly followed or cannot answer to quality of life
questionnaires because of psychological, social, familial or geographic reasons
9.Participation in another clinical trial with any investigational drug within
30 days prior to study enrolment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201600117960-NL |
| CCMO | NL65862.091.18 |