Trial Evaluating the Safety of 2 Schedules of Cabazitaxel in Elderly Men With mCRPC Previously Treated With a Docetaxel

  • STATUS
    Recruiting
  • End date
    Jul 23, 2022
  • participants needed
    170
  • sponsor
    Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Updated on 23 January 2021
Investigator
Reza ELAIDI, PhD
Primary Contact
Urologie und Kinderurologie Marienkrankenhaus Bergisch (9.7 mi away) Contact
+53 other location
platelet count
gonadotropin
prednisone
testosterone
progressive disease
neutrophil count
docetaxel
cabazitaxel
surgical castration

Summary

The purpose of this study is to evaluate the incidence of grade 3 neutropenia 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.

Description

Randomized, open-label, phase 3 trial in mCRPC patients aged 65 years.

Number of subjects:

Total:170 (85 per arm)

Treatment
  • Arm A : cabazitaxel 25 mg/m on Day 1 of a 3-week cycle plus daily prednisone or
  • Arm B: cabazitaxel 16 mg/m on Day 1 and Day 15 of a 4-week cycle plus daily prednisone.
  • Treatment will be continued for a maximum of 10 cycles unless there is documented disease progression or unacceptable toxicity.
  • Standard cabazitaxel premedication will be used
  • Prophylactic G-CSF (GRANOCYTE) will be injected from Day 3 to Day 7 after every administration cycle of cabazitaxel All new hormonal treatment, including ODM-201, prior to study entry is allowed.
  • Patients who received Radium-223 are eligible for this study
  • Treatment with LHRH should not be discontinued.

Exploratory assessments:

CT-Scan (abdominal/pelvic/chest) or whole body MRI and Bone scan: at screening, every 3 months and EOT.

FACT-P questionnaire:at C1D1,each subsequent visit and EOT

Exploratory substudy Blood samples will be collected in France (4 or 6 sites) and the Netherlands (2 sites). Biomarker analysis will be conducted at the Urology and The Tumor Immunology Laboratory at Radboud UMC in NL.

Biomarker schedule Arm A (25mg/m2): Baseline - Week 6 - Week 12 - at progression Arm B (16mg/m2): Baseline - Week 6 - Week 12 - at progression Optional sample points are at C1D8.

Number of subjects: 50

Statistical analysis:

A sample size of 77 evaluable patients per arm will achieve 80% power to detect a 20% difference in G3 neutropenia incidence between the 2 arms. The incidence in group cabazitaxel 25 mg/m2 q3w is assumed to be 32% and 12% on bi-weekly cabazitaxel arm. The test used is a two-sided Fisher's exact test at 0.05 significance level. Assuming 10% non-evaluable patients, 85 patients should be included in each arm for a total of 170. Patients will be stratified according to G8 score(< 14 vs. 14), and age (< 70 vs. 70) before randomization.

Exploratory sub-study The trial is powered on a clinical endpoint, namely to detect a 20% difference in G3 neutropenia incidence between arms (32% in arm A vs 12% arm B; power 80% with two-sided alpha of 5%, correcting for 10% non-evaluable patients (=17 patients).

From the 153 evaluable patients, we have 76 patients in each arm, of which we expect 50-60 evaluable patients for translational studies (calculations performed on 25 per arm).

In arm A we expect 8 patients (32% of patients) with G3 neutropenia, and 17 patients that do not. In arm B we expect 3 patients (12% of patients) with G3 neutropenia, and 22 patients that do not. For the MDSC analyses, we therefore will be comparing 11 patients with G3 neutropenia to 39 patients.

For all continuous variables, including all immune subpopulations present in blood, mean (sd) will be presented if the distribution seems to be symmetric and in case of a skewed distribution the median and IQR. For categorical data, number and percentage will be presented. For comparison of continuous data linear regression analyses or correlation (Spearman or Pearson) will used. For comparison of continuous data with categorical data logistic regression analysis will be used. For comparison of two sets of categorical data the chi-square test of Fisher"s exact test will be utilized. For the radiological PFS analyses the estimates of the hazard ratio and corresponding 95% confidence interval will be tested using a Cox Proportional hazard model. For the overall survival, a stratified log-rank test will be used to compare between groups.

Details
Condition Metastatic Prostate Cancer, Prostate Cancer Metastatic
Treatment prednisone, Cabazitaxel, granulocyte colony-stimulating factor (G-CSF)
Clinical Study IdentifierNCT02961257
SponsorAssociation Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Patient aged 65 years with mCRPC previously treated with docetaxel
Medical or surgical castration with castrate level of testosterone (< 50 ng/dl) based on the EAU definition of castrate level of testosterone
Progressive disease according to PCWG2
Histologically proven prostate carcinoma
Health status allowing use of chemotherapy: G8 > 14; or G8 score 14 with geriatric assessment concluding to reversible impairment allowing use of chemotherapy
ECOG-PS 0, 1 or 2(ECOG-PS 2 should be related to prostate cancer)
Adequate hematologic, liver and renal functions
Neutrophil count 1.5 109/L
Haemoglobin 10 g/ dL
Platelet count 100.109/L
Total bilirubin 1 the upper limit of normal (ULN)
Transaminases 1.5 ULN
Serum creatinine 2.0 ULN
Ongoing LHRH therapy at study entry
Signed informed consent

Exclusion Criteria

History of severe hypersensitivity reaction (grade 3) to docetaxel
History of severe hypersensitivity reaction (grade 3) to polysorbate 80 containing drugs
Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
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)
PS >2 not related to prostate cancer disease
G8 14 with geriatric assessment contra-indicating standard cabazitaxel regimen
Concomitant vaccination with yellow fever vaccine
Patient who cannot be regularly followed or cannot answer to quality of life questionnaires because of psychological, social, familial or geographic reasons
Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment
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