Trial document




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  DRKS00017467

Trial Description

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Title

Randomized multicenter, phase III trial evaluating the safety of 2 schedules of cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men (≥ 65years) with metastatic castration resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen

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Trial Acronym

CABASTY

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URL of the Trial

http:///

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Brief Summary in Lay Language

Patients suffer from a metastatic prostate cancer that does not respond to medical castration. They have already received chemotherapy based on docetaxel, which was unsuccessful, and are at least 65 years old.
Cabazitaxel is usually prescribed with corticosteroids (prednisone or prednisolone) for the treatment of non-hormonal prostate cancer, which has already been treated with docetaxel-type chemotherapy.

In order to reduce the risk of infection possibly associated with a decrease in the number of white blood cells (neutrophil count), after each cabazitaxel injection, a growth factor (G-CSF) is administered via a subcutaneous (= under the skin) injection to stimulate white blood cell production. Granulocyte Colony Stimulating Factor (G-CSF) is used as a preventative treatment to stimulate white blood cell proliferation and is routinely used in chemotherapy (such as cabazitaxel).

The slightly more pronounced hematotoxicity ("poisoning" of the blood) of cabazitaxel medication over docetaxel is the reason to examine whether a comparative study with less than the standard dose can achieve the same oncological results with less (febrile) neutropenia.
Febrile neutropenia is a replacement for severe infections. The fever associated with chemotherapy-associated neutropenia is due to infection in 95 percent of patients, although more than half have no germ.

Patients are randomly assigned to one of the two study arms (standard therapy / arm A or comparison group / arm B) by means of a computer program.

The main objective of this study is to assess the occurrence of a decrease in the number of certain white blood cells and / or the associated difficulties (fever and infections).

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Brief Summary in Scientific Language

There is increasing evidence that older men have more aggressive prostate cancer. Currently, physicians are treating elderly patients with metastatic castration-resistant prostate cancer (mCRPC) with new androgen receptor (AR) -based drugs, such as abiraterone acetate or enzalutamide, as they have been shown to prolong overall survival. However, as prostate cancer is a heterogeneous disease, not all patients respond to AR-targeted drugs.
Cabasty is an international, randomized, multi-center phase III study that randomizes 2 different dosages of cabazitaxel + prednisolone in older men with castration-resistant metastatic prostate cancer.
Cabazitaxel is an approved medication for patients with treatment failure after docetaxel. However, the dose is associated with a high incidence of neutropenia grade ≥3. The slightly more pronounced hematotoxicity of this medication compared to docetaxel provided the opportunity to examine whether in a randomized setting with less than the standard dose, the same oncological results could be achieved with less (febrile) neutropenia.
We would like to confirm the improved safety profile of the two-week treatment with cabazitaxel in this randomized trial, in which cabazitaxel 25 mg / m2 every 3 weeks compared to cabazitaxel 16 mg / m2 every 2 weeks until disease progression or unacceptable toxicity.
G-CSF is systematically given to each patient at low risk in each cycle.
A total of 170, in Germany but only 45, patients ≥ 65 years of age with prior docetaxel medication who are castration-resistant metastases should be included in the clinical trial. The clinical condition must allow chemotherapy according to the inclusion and exclusion criteria.

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Organizational Data

  •   DRKS00017467
  •   2019/06/12
  •   2016/10/02
  •   yes
  •   Approved
  •   149/18, Ethikkommission der Medizinischen Fakultät der Otto-von-Guericke-Universität Magdeburg
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Secondary IDs

  •   U1111-1234-7851 
  •   2016-001179-60 
  •   NCT02961257  (ClinicalTrials.gov)
  •   RECF3245  (French Register)
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Health Condition or Problem studied

  •   C61 -  Malignant neoplasm of prostate
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Interventions/Observational Groups

  •   Arm A : cabazitaxel 25 mg/m² on Day 1 of a 3-week cycle plus daily prednisone (10 mg)

    - 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 (5 days) after every administration 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.
  •   Arm B: cabazitaxel 16 mg/m² on Day 1 and Day 15 of a 4-week cycle plus daily prednisone (10 mg)

    - 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 (5 days) after every administration 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.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   No
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Primary Outcome

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.

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Secondary Outcome

- Maximum PSA change from baseline at any time using waterfall plot (PCWG2). The percentage of patients with a ≥ 30% and ≥50% decrease from baseline will be derived from this waterfall plot.
- Time to PSA progression as per PCWG2 criterion (time to first PSA increase that is ≥25% and ≥2 ng/mL above the nadir, and which is confirmed by a second value).
- Dose reductions and dose delays
- Radiological progression-free survival (rPFS) as per PCWG2 criterion (calculated from time to randomization and defined by modified RECIST criteria 1. or the appearance of 2 new lesions on a bone scan, confirmed by a bone scan 6 weeks later).
- Time to first Skeletal-Related Event: time from randomization to the occurrence of the first skeletal-related event (radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain)- Incidence of SREs (radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression)
- Time to opioid treatment: time from randomization to the first use of opioid treatment (if pertinent)
- FACT-P (Functional Assessment of Cancer Therapy – Prostate): 27 core items to assess patient function in four domains (physical, social/family, emotional, and functional wellbeing) and supplemented by 12 specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score. Higher scores represent better quality of life. Patients are defined as having a quality-of-life response if they have a 10-point improvement in their global FACT-P score, as compared with baseline, on two consecutive measurements obtained at least three weeks apart.
- Overall survival: time from randomization to death from any cause in the intent to treat population.
- Time to onset of grade ≥ 3 neutropenia
Grade ≥3 neutropenia duration ( from date of onset of grade ≥ 3 until grade ≤ 2)
Incidence of grade ≥ 3 neutropenia and/or neutropenic complications by cycle
- Adverse events, serious adverse events and discontinuation for adverse events

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Countries of Recruitment

  •   France
  •   Germany
  •   Netherlands
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Locations of Recruitment

  • University Medical Center 
  • Doctor's Practice 
  • Doctor's Practice 
  • Medical Center 
  • Doctor's Practice 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2019/05/08
  •   170
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Male
  •   65   Years
  •   no maximum age
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Additional 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

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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.

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Addresses

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    • Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie (ARTIC)Georges Pompidou European Hospital
    • 20 rue Leblanc
    • 75908  Paris Cedex 15
    • France
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    • Universitätsklinik für Urologie und Kinderurologie
    • Mr.  Prof. Dr. med.  Martin  Schostak 
    • Leipziger Str. 44
    • 39120  Magdeburg
    • Germany
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    • Universitätsklinik für Urologie und Kinderurologie
    • Mr.  Prof. Dr. med.  Martin  Schostak 
    • Leipziger Str. 44
    • 39120  Magdeburg
    • Germany
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Sources of Monetary or Material Support

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    • Sanofi-aventis groupe
    • 54, rue La Boétie
    • 75008  Paris
    • France
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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