Clinical Trials List
Protocol NumberEFC11785
2012-09-01 - 2018-01-04
Phase III
Terminated2
Study ended1
ICD-10Z51.11
Encounter for antineoplastic chemotherapy
ICD-9V58.1
Encounter for chemotherapy
Randomized, Open Label Multi-Center Study Comparing Cabazitaxel at 20 mg/m² and at 25 mg/m² Every 3 Weeks in Combination with Prednisone for the Treatment of Metastatic Castration Resistant Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen
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Trial Applicant
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Sponsor
Sanofi
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Peng-Chan Lin Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Wen-Pin Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Su-Peng Yeh Division of Hematology & Oncology
Condition/Disease
Metastatic Castration Resistant Prostate Cancer
Objectives
Primary Objective
To demonstrate the non inferiority in term of overall survival (OS) of cabazitaxel 20 mg/m²
(Arm A) versus cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in patients
with metastatic castration resistant prostate cancer (MCRPC) previously treated with a
docetaxel-containing regimen.
Secondary Objective(s)
• To evaluate safety in the 2 treatment arms and to assess if cabazitaxel 20 mg/m² is
better tolerated than cabazitaxel 25 mg/m².
• To compare efficacy of cabazitaxel at 20 mg/m² and 25 mg/m² for:
− Progression Free Survival (PFS) defined as the first occurrence of any of the
following events: tumor progression per Response Evaluation Criteria In Solid
Tumors (RECIST), PSA progression, pain progression or death due to any cause
− Prostate-Specific Antigen (PSA)-Progression
− Pain progression
− Tumor response in patients with measurable disease (RECIST 1.1).
− PSA response
− Pain response in patients with stable pain at baseline.
• To compare Health-related Quality of Life (HRQL)
• To assess the pharmacokinetics and pharmacogenomics of cabazitaxel
Test Drug
XRP6258
Active Ingredient
Cabazitaxel
Dosage Form
IV injection
Dosage
1.5
Endpoints
PRIMARY
To demonstrate the non inferiority in term of overall survival (OS) of cabazitaxel 20 mg/m² (Arm
A) versus cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in patients with
metastatic castration resistant prostate cancer previously treated with a docetaxel-containing
regimen.
SECONDARY
• To evaluate safety in the 2 treatment arms and to assess if cabazitaxel 20 mg/m² is better
tolerated than cabazitaxel 25 mg/m².
• To compare efficacy of cabazitaxel at 20 mg/m² and 25 mg/m² for:
- Progression Free Survival (PFS) defined as the first occurrence of any of the following
events: tumor progression per Response Evaluation Criteria In Solid Tumors
(RECIST 1.1) (6), PSA progression, pain progression or death due to any cause.
- PSA-Progression.
- Pain progression.
- Tumor response in patients with measurable disease (RECIST 1.1).
- PSA response.
- Pain response in patients with stable pain at baseline.
• To compare Health-related Quality of Life (HRQL).
• To assess the pharmacokinetics and pharmacogenomics of cabazitaxel.
EXPLORATORY OBJECTIVE
Collection of circulating free plasma DNA (total and tumor specific) for biomarker studies.
To demonstrate the non inferiority in term of overall survival (OS) of cabazitaxel 20 mg/m² (Arm
A) versus cabazitaxel 25 mg/m² (Arm B) in combination with prednisone in patients with
metastatic castration resistant prostate cancer previously treated with a docetaxel-containing
regimen.
SECONDARY
• To evaluate safety in the 2 treatment arms and to assess if cabazitaxel 20 mg/m² is better
tolerated than cabazitaxel 25 mg/m².
• To compare efficacy of cabazitaxel at 20 mg/m² and 25 mg/m² for:
- Progression Free Survival (PFS) defined as the first occurrence of any of the following
events: tumor progression per Response Evaluation Criteria In Solid Tumors
(RECIST 1.1) (6), PSA progression, pain progression or death due to any cause.
- PSA-Progression.
- Pain progression.
- Tumor response in patients with measurable disease (RECIST 1.1).
- PSA response.
- Pain response in patients with stable pain at baseline.
• To compare Health-related Quality of Life (HRQL).
• To assess the pharmacokinetics and pharmacogenomics of cabazitaxel.
EXPLORATORY OBJECTIVE
Collection of circulating free plasma DNA (total and tumor specific) for biomarker studies.
Inclution Criteria
Patients meeting all the following criteria will be considered eligible for enrolment into the study:
I 01. Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that is
resistant to hormone therapy and previously treated with a docetaxel-containing regimen.
Patient must have documented progression of disease during or within 6 months after prior
hormone therapy and disease progression during or after docetaxel-containing therapy.
I 02. Patient must have either measurable or non-measurable disease:
• Patient with measurable disease must have documented progression of disease by
RECIST 1.1 criteria. Previously irradiated lesions, primary prostate lesion, and bone
lesions will be considered non-measurable disease.
• Patient with non-measurable disease must have documented rising PSA levels or
appearance of new lesions (≥2 new lesions on 2 sequential bone scans if PD diagnosed on
bone scan only). [Rising PSA is defined as at least two consecutive rises in PSA to be
documented over a reference value (measure 1) taken at least one week apart. The first
rising PSA (measure 2) should be taken at least 7 days after the reference value. A third
confirmatory PSA measure is required (2nd beyond the reference level) to be greater than
the second measure and it must be obtained at least 7 days after the 2nd measure. If this is
not the case, a fourth PSA measure is required to be taken and be greater than the 2nd
measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior
to randomization]. In case of progression based on PSA level increase only, patients
should have received a cumulative dose of at least 225 mg/m² or 3 cycles of docetaxel
(early PSA level increase should not be considered as progression).
I 03. Received prior castration by orchiectomy and/or Luteinizing Hormone-Releasing Hormone
(LH-RH) agonist or antagonist with or without antiandrogen, antiandrogen withdrawal,
monotherapy with estramustine, or other hormonal agents. (A prior treatment by
antiandrogen is not mandatory. However, if the patient has been treated with
antiandrogens, and PSA is above 5 ng/mL at the last administration of antiandrogens,
presence or absence of antiandrogen withdrawal syndrome* should be confirmed prior to
the study entry). (LH-RH agonist or antagonist treatment should continue during the study
treatment period. Chlormadinone acetate or flutamide must have been stopped at least 4
weeks prior to, while bicalutamide must have been stopped at least 6 weeks prior to, the
last PSA evaluation.) (* The antiandrogen withdrawal syndrome is a decrease in PSA
seen upon stopping an antiandrogen such as chlormadinone acetate, flutamide, or
bicalutamide; this occurs because the antiandrogen has induced a mutation in the
androgen receptor which is allowing the antiandrogen to stimulate prostate cancer growth
rather than inhibit it).
I 04. Life expectancy >6 months.
I 05. Eastern Cooperative Oncology Group ECOG performance status (PS) 0 – 2 (ie, patient
must be ambulatory, capable of all self-care, and up and about more than 50% of waking
hours).
I 06. Age ≥18 years (or country’s legal age of majority if > 18 years)
I 01. Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that is
resistant to hormone therapy and previously treated with a docetaxel-containing regimen.
Patient must have documented progression of disease during or within 6 months after prior
hormone therapy and disease progression during or after docetaxel-containing therapy.
I 02. Patient must have either measurable or non-measurable disease:
• Patient with measurable disease must have documented progression of disease by
RECIST 1.1 criteria. Previously irradiated lesions, primary prostate lesion, and bone
lesions will be considered non-measurable disease.
• Patient with non-measurable disease must have documented rising PSA levels or
appearance of new lesions (≥2 new lesions on 2 sequential bone scans if PD diagnosed on
bone scan only). [Rising PSA is defined as at least two consecutive rises in PSA to be
documented over a reference value (measure 1) taken at least one week apart. The first
rising PSA (measure 2) should be taken at least 7 days after the reference value. A third
confirmatory PSA measure is required (2nd beyond the reference level) to be greater than
the second measure and it must be obtained at least 7 days after the 2nd measure. If this is
not the case, a fourth PSA measure is required to be taken and be greater than the 2nd
measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior
to randomization]. In case of progression based on PSA level increase only, patients
should have received a cumulative dose of at least 225 mg/m² or 3 cycles of docetaxel
(early PSA level increase should not be considered as progression).
I 03. Received prior castration by orchiectomy and/or Luteinizing Hormone-Releasing Hormone
(LH-RH) agonist or antagonist with or without antiandrogen, antiandrogen withdrawal,
monotherapy with estramustine, or other hormonal agents. (A prior treatment by
antiandrogen is not mandatory. However, if the patient has been treated with
antiandrogens, and PSA is above 5 ng/mL at the last administration of antiandrogens,
presence or absence of antiandrogen withdrawal syndrome* should be confirmed prior to
the study entry). (LH-RH agonist or antagonist treatment should continue during the study
treatment period. Chlormadinone acetate or flutamide must have been stopped at least 4
weeks prior to, while bicalutamide must have been stopped at least 6 weeks prior to, the
last PSA evaluation.) (* The antiandrogen withdrawal syndrome is a decrease in PSA
seen upon stopping an antiandrogen such as chlormadinone acetate, flutamide, or
bicalutamide; this occurs because the antiandrogen has induced a mutation in the
androgen receptor which is allowing the antiandrogen to stimulate prostate cancer growth
rather than inhibit it).
I 04. Life expectancy >6 months.
I 05. Eastern Cooperative Oncology Group ECOG performance status (PS) 0 – 2 (ie, patient
must be ambulatory, capable of all self-care, and up and about more than 50% of waking
hours).
I 06. Age ≥18 years (or country’s legal age of majority if > 18 years)
Exclusion Criteria
Patients who have met all the above inclusion criteria will be screened for the following exclusion
criteria which are sorted and numbered in the following three sub-sections:
7.3.1 Exclusion criteria related to study methodology
E 01. Previous treatment with mitoxantrone or cabazitaxel.
E 02. Prior isotope therapy, whole pelvic radiotherapy or radiotherapy to >30% of bone marrow.
E 03. Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from
any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology
Criteria (NCI CTCAE) v4.03) at the time of randomization.
E 04. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to
enrollment in the study.
E 05. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis,
pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which
chemotherapy has been completed ≥ 5 years ago and from which the patient has been
disease-free for ≥5 years.
E 06. Participation in another clinical trial and any concurrent treatment with any investigational
drug within 30 days prior to randomization.
E 07. Known brain or leptomeningeal involvement.
E 08. Other concurrent serious illness or medical conditions.
E 09. Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of
congestive heart failure (NYHA III or IV) or myocardial infarction within last 6 months is
also not allowed.
E 10. Any severe acute or chronic medical condition which could impair the ability of the patient
to participate to the study or to comply with the study procedures or interfere with
interpretation of study results.
E 11. Absence of signed and dated Institutional Review Board (IRB)-approved patient informed
consent form prior to enrollment into the study.
E 12. Patients with reproductive potential who do not agree to use accepted and effective method
of contraception during the study treatment period. The definition of “effective method of
contraception” will be based on the investigator’s judgment.
Patients' Partners of childbearing potential (unless surgically sterile, post menopausal or
for another reason have no chance of becoming pregnant) not protected by highly
effective contraceptive method of birth control as defined for contraception in the
Informed Consent Form and /or in a local protocol addendum.
7.3.2 Exclusion criteria related to chemotherapy
E 13. History of severe (>grade 2) hypersensitivity to docetaxel, or polysorbate 80.
E 14. Inadequate organ and bone marrow function as evidenced by:
a. Hemoglobin <9 g/dL
b. Absolute neutrophil count <1.5 x 109/L
c. Platelet count < 100 x 109/L
d. AST/SGOT and/or ALT/SGPT > 1.5 x ULN;
e. Total bilirubin > 1.0 x ULN
f. Serum Creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance
will be calculated according to CKD-EPI formula and creatinine clearance
<60 mL/min will exclude the patient (see Appendix A for calculation formula)
E 15. Contraindications to the use of corticosteroid treatment.
E 16. Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common
Terminology Criteria [NCI CTCAE] v.4.03
criteria which are sorted and numbered in the following three sub-sections:
7.3.1 Exclusion criteria related to study methodology
E 01. Previous treatment with mitoxantrone or cabazitaxel.
E 02. Prior isotope therapy, whole pelvic radiotherapy or radiotherapy to >30% of bone marrow.
E 03. Adverse events (excluding alopecia and those listed in the specific exclusion criteria) from
any prior anticancer therapy of grade >1(National Cancer Institute Common Terminology
Criteria (NCI CTCAE) v4.03) at the time of randomization.
E 04. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 4 weeks prior to
enrollment in the study.
E 05. Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis,
pTa, and pT1) bladder cancer are allowed, as well as any other cancer for which
chemotherapy has been completed ≥ 5 years ago and from which the patient has been
disease-free for ≥5 years.
E 06. Participation in another clinical trial and any concurrent treatment with any investigational
drug within 30 days prior to randomization.
E 07. Known brain or leptomeningeal involvement.
E 08. Other concurrent serious illness or medical conditions.
E 09. Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of
congestive heart failure (NYHA III or IV) or myocardial infarction within last 6 months is
also not allowed.
E 10. Any severe acute or chronic medical condition which could impair the ability of the patient
to participate to the study or to comply with the study procedures or interfere with
interpretation of study results.
E 11. Absence of signed and dated Institutional Review Board (IRB)-approved patient informed
consent form prior to enrollment into the study.
E 12. Patients with reproductive potential who do not agree to use accepted and effective method
of contraception during the study treatment period. The definition of “effective method of
contraception” will be based on the investigator’s judgment.
Patients' Partners of childbearing potential (unless surgically sterile, post menopausal or
for another reason have no chance of becoming pregnant) not protected by highly
effective contraceptive method of birth control as defined for contraception in the
Informed Consent Form and /or in a local protocol addendum.
7.3.2 Exclusion criteria related to chemotherapy
E 13. History of severe (>grade 2) hypersensitivity to docetaxel, or polysorbate 80.
E 14. Inadequate organ and bone marrow function as evidenced by:
a. Hemoglobin <9 g/dL
b. Absolute neutrophil count <1.5 x 109/L
c. Platelet count < 100 x 109/L
d. AST/SGOT and/or ALT/SGPT > 1.5 x ULN;
e. Total bilirubin > 1.0 x ULN
f. Serum Creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance
will be calculated according to CKD-EPI formula and creatinine clearance
<60 mL/min will exclude the patient (see Appendix A for calculation formula)
E 15. Contraindications to the use of corticosteroid treatment.
E 16. Symptomatic peripheral neuropathy grade >2 (National Cancer Institute Common
Terminology Criteria [NCI CTCAE] v.4.03
The Estimated Number of Participants
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Taiwan
10 participants
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Global
1200 participants
