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

NCT ID: NCT02961257

Last Updated: 2022-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-05
• Study Completion Date: 2021-12-02

Brief 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.

Detailed Description

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

Number of subjects:

Total:170 to 200 (85 to 100 per arm)

Treatment:

• Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone or
• Arm B: cabazitaxel 16 mg/m² 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 to 90 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 to 100 patients should be included in each arm for a total of 170 to 200.

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 nThe 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 to 180 evaluable patients, we have 76 to 90 patients in each arm, of which we expect 40-60 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.

Conditions

Prostate Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Cabazitaxel 25 mg/m² intravenously over 1 hour on Day 1of a 3-week cycle, plus prednisone (or prednisolone) 10 mg orally given daily for a maximum of 10 cycles (ie 30 weeks of treatment).

Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.

Group Type: EXPERIMENTAL

cabazitaxel

Intervention Type: DRUG

• Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone or
• Arm B: cabazitaxel 16 mg/m² 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

Prednisone

Intervention Type: DRUG

Arm A:plus prednisone 10 mg orally given daily for a maximum of 10 cycles Arm B: plus prednisone 10 mg orally given per day up to 10 cycles

Granulocyte colony-stimulating factor (G-CSF)

Intervention Type: DRUG

Primary prophylaxis with Granulocyte Colony-Stimulating Factor (G-CSF) will be injected from Day 3 to Day 7 after every administration of cabazitaxel

Arm B

Cabazitaxel 16 mg/m2 on Day 1 and Day 15 of a 4-week cycle plus prednisone (or prednisolone) 10 mg per day up to 10 cycles (ie 40 weeks of treatment). Prophylactic Granulocyte colony-stimulating factor G-CSF (Granocyte) will be injected from Day 3 to Day 7 after every administration of cabazitaxel.

Group Type: EXPERIMENTAL

cabazitaxel

Intervention Type: DRUG

• Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone or
• Arm B: cabazitaxel 16 mg/m² 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

Prednisone

Intervention Type: DRUG

Arm A:plus prednisone 10 mg orally given daily for a maximum of 10 cycles Arm B: plus prednisone 10 mg orally given per day up to 10 cycles

Granulocyte colony-stimulating factor (G-CSF)

Intervention Type: DRUG

Primary prophylaxis with Granulocyte Colony-Stimulating Factor (G-CSF) will be injected from Day 3 to Day 7 after every administration of cabazitaxel

Interventions

cabazitaxel

• Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone or
• Arm B: cabazitaxel 16 mg/m² 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

Intervention Type: DRUG

Prednisone

Arm A:plus prednisone 10 mg orally given daily for a maximum of 10 cycles Arm B: plus prednisone 10 mg orally given per day up to 10 cycles

Intervention Type: DRUG

Granulocyte colony-stimulating factor (G-CSF)

Primary prophylaxis with Granulocyte Colony-Stimulating Factor (G-CSF) will be injected from Day 3 to Day 7 after every administration of cabazitaxel

Intervention Type: DRUG

Other Intervention Names

Jevtana; XRP6258; Granocyte

Eligibility Criteria

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

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:

1. Neutrophil count ≥1.5 109/L

2. Haemoglobin ≥10 g/ dL

3. Platelet count ≥100.109/L

4. Total bilirubin ≤ 1 the upper limit of normal (ULN)

5. Transaminases ≤ 1.5 ULN

6. 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. 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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephane OUDARD, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges Pompidou, Oncology Department

Locations

Hôpital Jean Minjoz

Besançon, , France

Hôpital Saint André, CHU de Bordeaux

Bordeaux, , France

Clinique Pasteur-CFRO

Brest, , France

Centre Maurice Tubiana

Caen, , France

Polyclinique Saint-Côme

Compiègne, , France

CHU Henri-Mondor

Créteil, , France

Clinique Victor Hugo

Le Mans, , France

Centre Oscar Lambret Lille

Lille, , France

Hôpital Belle-Isle

Metz, , France

GHIRM

Montfermeil, , France

Institut de Cancérologie du Gard - CHU

Nîmes, , France

Institut Mutualiste Montsouris

Paris, , France

Hôpital Européen Georges Pompidou

Paris, , France

Hôpital Universitaire Tenon

Paris, , France

Hôpital Cochin

Paris, , France

CHU de Poitiers

Poitiers, , France

CHU de Rouen

Rouen, , France

Clinique Armoricaine de Radiologie

Saint-Brieuc, , France

HIA Bégin 69 avenue de Paris

Saint-Mandé, , France

Centre Hospitalier de Sens

Sens, , France

Hôpitaux universitaires de Strasbourg

Strasbourg, , France

Hôpital FOCH

Suresnes, , France

Centre de cancérologie Les Dentellières

Valenciennes, , France

Urologisch-onkologische Schwerpunktpraxis

Bernburg, , Germany

Uniklinik Köln, Urologie, Uro-Onkologie, spezielle urologische und Roboter-assistierte Chirurgie

Cologne, , Germany

Urologie und Kinderurologie Marienkrankenhaus Bergisch

Gladbach, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitäts-klinik für Urologie und Kinderurologie

Magdeburg, , Germany

Urologische Praxis am Hasselbachplatz

Magdeburg, , Germany

Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie,

Münster, , Germany

Studienpraxis Urologie

Nürtingen, , Germany

Countries

France; Germany

References

Oudard S, Ratta R, Voog E, Barthelemy P, Thiery-Vuillemin A, Bennamoun M, Hasbini A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Lange C, Phan L, Belhouari H, Tran Y, Kotti S, Helissey C. Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1629-1638. doi: 10.1001/jamaoncol.2023.4255.

Reference Type: DERIVED

PMID: 37883073 (View on PubMed)

Pobel C, Auclin E, Procureur A, Clement-Zhao A, Simonaggio A, Delanoy N, Vano YA, Thibault C, Oudard S. Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review. Future Oncol. 2021 Jan;17(1):91-102. doi: 10.2217/fon-2020-0672. Epub 2020 Dec 2.

Reference Type: DERIVED

PMID: 33463373 (View on PubMed)

Other Identifiers

CABASTY

Identifier Type: -

Identifier Source: org_study_id