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

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ClinicalTrials.gov Identifier: NCT02961257
Recruitment Status : Recruiting
First Posted : November 10, 2016
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: cabazitaxel Drug: Prednisone Drug: Granulocyte colony-stimulating factor (G-CSF) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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 mCRPC Previously Treated With a Docetaxel-containing Regimen
Actual Study Start Date : May 5, 2017
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Experimental: 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.

Drug: 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
Other Names:
  • Jevtana
  • XRP6258

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

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
Other Name: Granocyte

Experimental: 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.
Drug: 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
Other Names:
  • Jevtana
  • XRP6258

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

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
Other Name: Granocyte




Primary Outcome Measures :
  1. Number of grade ≥ 3 neutropenia and/or neutropenic complications [ Time Frame: Up to 11 months ]

    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.

    with two schedules of -+cabazitaxel (bi-weekly versus tri-weekly) plus prednisone in elderly men with mCRPC previously treated with a docetaxel-containing regimen



Secondary Outcome Measures :
  1. Dose reductions [ Time Frame: through study completion, an average of 40 weeks ]
    Up to 11 months

  2. Radiological progression-free survival (rPFS) [ Time Frame: Up to 11 months ]
    CT-Scan (abdominal/pelvic/chest) or whole body MRI and Bone scan

  3. Time to PSA progression [ Time Frame: Up to 11 months ]
    Assessed at C1D1, at every each subsequent visit and EOT

  4. Time to first symptomatic Skeletal-Related Event (SRE) and incidence of SREs [ Time Frame: Up to 11 months ]
    Assessed at C1D1, at every each subsequent visit and EOT

  5. Time to opioid treatment (if relevant) [ Time Frame: Up to 11 months ]
  6. Prostate-specific antigen (PSA) response rate [ Time Frame: Up to 11 months ]
    Assessed at C1D1, at every each subsequent visit and EOT

  7. Quality of Life (FACT-P) [ Time Frame: Up to 11 months ]
    Assessed at C1D1, at every each subsequent visit and EOT

  8. Objective response rate (ORR) in measurable lesions (RECIST criteria 1.1 - only on metastasis [ Time Frame: Up to 11 months ]
    CT-Scan (abdominal/pelvic/chest) or whole body MRI

  9. Overall Survival (OS) [ Time Frame: up to 11 months ]
  10. Factors influencing survival [ Time Frame: Up to 11 months ]
    Factors influencing survival (duration of response to first ADT, serum testosterone, cumulative dose of cabazitaxel, neutrophils/lymphocytes ratio, Gleason score, G8, grade ≥3 neutropenia)

  11. Time to onset of grade ≥3 neutropenia [ Time Frame: Up to 11 months ]
    Hematology every week until EOT

  12. Grade ≥3 neutropenia duration ( from date of onset of grade ≥ 3 until grade ≤ 2) [ Time Frame: Up to 11 months ]
    Hematology every week until EOT

  13. Time to onset of grade ≥3 neutropenia by cycle [ Time Frame: Up to 11 months ]
    Analysis of grade ≥3 neutropenia and/or neutropenia by cycle

  14. Adverse events [ Time Frame: Up to 11 months ]
  15. Dose delay [ Time Frame: Up to 11 months ]

Other Outcome Measures:
  1. Proportion of patients achieving a best objective response of SD, PR or CR according to RECIST 1.1 specifically comparing those achieving >30% and >50% decrease in MDSC post-induction compared to those who did not achieve this reduction. [ Time Frame: Up to 6 months ]
    Biomarker analysis

  2. Proportion of patients achieving a >50% PSA response at 12 weeks and at any time specifically comparing those achieving >30% and >50% decrease in MDSC post-induction compared to those who did not achieve this reduction. [ Time Frame: Up to 6 months ]
    Exploratory sub-study: biomarker analysis

  3. Radiological progression-free survival (rPFS) according to PCWG2 criteria for all patients, in relation to percentage MDSC change (% maximum change and those achieving >30% and >50% decrease) [ Time Frame: Up to 6 months ]
    Exploratory sub-study: biomarker analysis

  4. Correlations between extent of MDSC (continuous) and NLR decline (continuous) [ Time Frame: Up to 6 months ]
    Exploratory sub-study: biomarker analysis

  5. Differences in peripheral blood immune populations (MDSCs, regulatory T-cells, T-effector and natural killer [NK] cells) with cabazitaxel responsiveness for Q2W and Q3W dosing schedule at week 6 and week 12 [ Time Frame: Up to 6 months ]

    biomarkers analysis

    1. collection of blood (EDTA tube) at Baseline, C1D8,week 6, week 12 and EOT Collection of blood (RNA Paxgene): baseline
    2. platelet poor plasma isolation, PBMC isolation, PMN isolation and
    3. Flow cytometry assessments and FACS sorting Next-generation targeted sequencing of cfDNA RNA sequencing of baseline PaxGene

  6. correlation between MDSC decline (>30% or >50%) with neutropenia (presence or absence) [ Time Frame: Up to 6 months ]

    Hematology every week until EOT

    1. collection of blood (EDTA tube) at Baseline, C1D8,week 6, week 12 and EOT Collection of blood (RNA Paxgene): baseline
    2. platelet poor plasma isolation, PBMC isolation, PMN isolation and
    3. Flow cytometry assessments and FACS sorting Next-generation targeted sequencing of cfDNA RNA sequencing of baseline PaxGene

  7. Associations between cabazitaxel dose, presence of neutropenia (C1D8), NLR conversion (wk6 and wk12) and MDSC decline (wk6 and wk12) [ Time Frame: Up to 6 months ]

    biomarkers analysis

    1. collection of blood (EDTA tube) at Baseline, C1D8,week 6, week 12 and EOT Collection of blood (RNA Paxgene): baseline
    2. platelet poor plasma isolation, PBMC isolation, PMN isolation and
    3. Flow cytometry assessments and FACS sorting Next-generation targeted sequencing of cfDNA RNA sequencing of baseline PaxGene

  8. To evaluate changes in peripheral blood immune populations at failure on cabazitaxel, with particular focus on CD38-positive MDSC subsets [ Time Frame: Up to 6 months ]

    biomarkers analysis

    1. collection of blood (EDTA tube) at Baseline, C1D8,week 6, week 12 and EOT Collection of blood (RNA Paxgene): baseline
    2. platelet poor plasma isolation, PBMC isolation, PMN isolation and
    3. Flow cytometry assessments and FACS sorting Next-generation targeted sequencing of cfDNA RNA sequencing of baseline PaxGene

  9. Associations between baseline MDSC and molecular underpinning (from cfDNA, specifically studying MYCN amplification and PTEN / TP53 aberration) [ Time Frame: Up to 6 months ]

    biomarkers analysis

    1. collection of blood (EDTA tube) at Baseline, C1D8,week 6, week 12 and EOT Collection of blood (RNA Paxgene): baseline
    2. platelet poor plasma isolation, PBMC isolation, PMN isolation and
    3. Flow cytometry assessments and FACS sorting Next-generation targeted sequencing of cfDNA RNA sequencing of baseline PaxGene



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02961257


Contacts
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Contact: Réza ELAIDI, PhD 00 33 (1)56 09 23 40 reza-thierry.elaidi-ext@aphp.fr
Contact: Houda BELHOUARI, MD houda.belhouari-ext@aphp.fr

Locations
Show Show 32 study locations
Sponsors and Collaborators
Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
Investigators
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Principal Investigator: Stephane OUDARD, MD, Ph.D Hôpital Européen Georges Pompidou, Oncology Department
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Responsible Party: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
ClinicalTrials.gov Identifier: NCT02961257    
Other Study ID Numbers: CABASTY
First Posted: November 10, 2016    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Prednisone
Sargramostim
Lenograstim
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Adjuvants, Immunologic