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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1128-5704 | Other Identifier | UTN |
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Primary Objectives:
Phase 1 Part:
To determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cabazitaxel as a single agent in pediatric participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To determine the objective response rate (complete and partial response) and the duration of response to cabazitaxel as a single agent in participants with recurrent or refractory high grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG).
Secondary Objectives:
Phase 1 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To characterize the pharmacokinetic (PK) profile of cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
To evaluate preliminary anti-tumor activity that may be associated with cabazitaxel in participants with recurrent or refractory solid tumors including tumors of the central nervous system.
Phase 2 Part:
To characterize the safety and tolerability of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
To estimate progression free survival in participants with recurrent or refractory HGG or DIPG.
To estimate overall survival in participants with recurrent or refractory HGG or DIPG.
To characterize the plasma PK profile of cabazitaxel in participants with recurrent or refractory HGG or DIPG.
The study duration will include a period for inclusion of up to 3 weeks and a 3-week treatment cycle(s). The participants may continue treatment until disease progression, unacceptable toxicity or willingness to stop followed by a minimum of 30-day follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1: Cabazitaxel 20 mg/m^2 | Experimental | Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression (DP) or discontinuation due to adverse event (AE) or death (from any cause). |
|
| Phase 1: Cabazitaxel 25 mg/m^2 | Experimental | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
| Phase 1: Cabazitaxel 30 mg/m^2 | Experimental | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
| Phase 1: Cabazitaxel 35 mg/m^2 | Experimental | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
| Phase 2: Cabazitaxel 30 mg/m^2 | Experimental | Cabazitaxel at the maximum tolerated dose (MTD) as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cabazitaxel (XRP6258) | Drug | Pharmaceutical form: Injection Route of administration: Intravenous |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1: Maximum Tolerated Dose of Cabazitaxel | MTD was highest dose level of cabazitaxel at which no more than 1 of 6 evaluable participants experienced dose limiting toxicities (DLT). DLT defined as an AE or abnormal laboratory values related to study treatment: hematologic DLTs: any Grade(G)4 hematologic toxicity except neutropenia G4 lasting≤7 days,G3 or 4 febrile neutropenia except G3 or 4 febrile neutropenia in absence of granulocyte-colony stimulating factor prophylaxis, G4 thrombocytopenia; non-hematologic DLTs:any G≥3 non-hematologic toxicity except G3 nausea or G3 or4 vomiting, G3 or4 diarrhea,G3 or4 dehydration,G3 fatigue lasting≤7 days, inadequately treated hypersensitivity reactions, elevated transaminases<10* upper limit of normal of ≤7 days, re-treatment delay of>2 weeks due to delayed recovery from toxicity related to study treatment to baseline G or≤ G1(except for alopecia) and platelet transfusion during Cycle1. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | Cycle 1 (21 days) |
| Phase 2: Percentage of Participants With Objective Response (OR) | OR in participants was defined as the participants with a Complete Response (CR) or Partial Response (PR) after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks. CR and PR were based on modified response assessment in neuro-oncology (RANO) criteria for participants with CNS tumors. CR was defined as disappearance of all target lesions. PR was defined as ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to the baseline measurement. | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
| Phase 2: Duration of Response (DOR) | DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. If progression or death was not observed, participant was censored at the date of participant's last progression-free tumor assessment prior to study cut-off date. PD as per RANO criteria was defined as ≥ 25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc.) plus any increase in tumor cross-sectional area (or tumor volume). |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. Treatment emergent adverse events (TEAEs) were defined as AEs that developed or worsened in grade or became serious during the on-treatment period which was defined as the period from the time of first dose of cabazitaxel until 30 days following the last administration of cabazitaxel. |
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Inclusion criteria:
Phase 1 Part (dose escalation): Participants with a histologically confirmed solid tumor including tumors of the central nervous system that was recurrent or refractory and for which no further effective standard treatment was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy.
Phase 2 Part (safety and activity): Participants with recurrent or refractory high grade glioma or diffuse intrinsic pontine glioma for whom no further effective therapy was available. All participants must had measurable disease. Participants with diffuse pontine glioma were eligible without a biopsy after evidence of progressive disease post radiation therapy. Participants with a grade III or grade IV glioma must had pathologic confirmation either at the time of initial diagnosis or at the time of recurrence.
Participants aged ≥2 years and ≤18 years
Participants met the body surface area (BSA) requirements to be eligible:
Performance status by:
Participants must had adequate liver, renal and marrow function as defined below:
Female participants of child-bearing potential must had a negative pregnancy test ≤7 days before starting cabazitaxel treatment.
Male and female participants of reproductive potential must agreed to use adequate contraception prior to study entry, for the duration of study participation and for 6 months following the last dose of cabazitaxel.
Written informed consent/assent prior to any study-specific procedures. Consent must be obtained from the participant and/or parent(s) or legal guardian(s) and the signature of at least one parent or guardian was required. Investigators also obtained assent of participants according to local, regional or national guidelines.
Participants must have recovered from the acute toxic effects of all prior therapy to ≤ grade 1 before entering the study.
Exclusion criteria:
Prior treatment within the following timeframes:
Prior systemic radioisotope therapy (this did not include diagnostic imaging or radioimmunoconjugates lacking myelosuppressive properties) or total body irradiation.
Prior bone marrow or stem cell transplant
Participants with any clinically significant illness that, in the investigator's opinion, could not be adequately controlled with appropriate therapy, would compromise a participant's ability to tolerate cabazitaxel or result in inability to assess toxicity. This included, but was not limited to uncontrolled intercurrent illness including ongoing or active infection, cardiac disease, renal impairment, planned surgery or psychiatric illness/social situations that would limit compliance with study requirements.
Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency-syndrome (AIDS)-related disease Known history of hepatitis C or known active hepatitis B infection. Pregnant or breast feeding women Treatment with strong inhibitors or strong inducers of CYP3A4 or enzyme inducing anti-epileptic drugs (EIAED) within 14 days prior to first dose of cabazitaxel and for the duration of study. Non-EIAEDs were permitted.
Known history of hypersensitivity to taxanes or polysorbate 80 or G-CSF. Participation in another interventional clinical trial and/or concurrent treatment with any investigational drug.
Participants not able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 840009 | Phoenix | Arizona | 85006 | United States | ||
| Investigational Site Number 840013 |
Phase I was a dose escalation part of Cabazitaxel to determine maximum tolerated dose (MTD). Phase 2 was efficacy and safety evaluation of Cabazitaxel at the MTD, determined in Phase 1.
Participants were enrolled at 12 centers between February 2013 and March 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1: Cabazitaxel 20 mg/m^2 | Cabazitaxel 20 mg/m^2 intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression (DP) or discontinuation due to adverse events (AE) or death (from any cause). |
| FG001 | Phase 1: Cabazitaxel 25 mg/m^2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 |
|
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|
|
| Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
| Baseline up to DP or death due to any cause (maximum duration: 112.1 weeks for Phase 1 and 12.1 weeks for Phase 2) |
| Phase 1: Number of Participants With Objective Response | OR in participants was defined as the participants with a CR or PR after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and RANO criteria for CNS tumors. For solid tumors, as per RECIST 1.1, CR defined as disappearance of all target and non-target lesions (any pathological lymph nodes, must had reduction in short axis to <10 mm); PR defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. For CNS tumors, as per RANO criteria, CR defined as disappearance of all target and non-target lesions; PR defined as a ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to baseline measurement. | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 112.1 weeks) |
| Phase 1 and 2: Pharmacokinetics (PK) Parameter of Cabazitaxel: Area Under the Plasma Concentration (AUC) Versus Time Curve | Blood samples for PK parameters were collected at 5 minutes before end of infusion (EOI), 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
| Phase 1 and 2: PK Parameter of Cabazitaxel: Total Plasma Clearance (CL) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
| Phase 1 and 2: PK Parameter of Cabazitaxel: Volume of Distribution at Steady State (Vss) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
| Phase 1 and 2: PK Parameter of Cabazitaxel: Maximum Plasma Concentration Observed (Cmax) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
| Phase 2: Progression Free Survival (PFS) | The PFS was defined as the time (in months) from the date of first dose administration until the date of first documented PD or death (from any cause), whichever came first. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. PD as per RANO criteria was defined as ≥25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc) plus any increase in tumor cross-sectional area (or tumor volume). The analysis was performed by Kaplan-Meier method. | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
| Phase 2: Overall Survival (OS) | OS was defined as the time (in months) from the date of first dose administration until the date of death (from any cause). If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive and the study cut-off date. The analysis was performed by Kaplan-Meier method. | Baseline up to death or study cut-off (maximum duration: 12.1 weeks) |
| Los Angeles |
| California |
| 90027 |
| United States |
| Investigational Site Number 840014 | Palo Alto | California | United States |
| Investigational Site Number 840007 | Aurora | Colorado | 80045 | United States |
| Investigational Site Number 840011 | Washington D.C. | District of Columbia | 20010 | United States |
| Investigational Site Number 840005 | Orlando | Florida | 32806 | United States |
| Investigational Site Number 840012 | Chicago | Illinois | 60611 | United States |
| Investigational Site Number 840010 | Baltimore | Maryland | 21287 | United States |
| Investigational Site Number 840002 | Boston | Massachusetts | 02115 | United States |
| Investigational Site Number 840003 | New York | New York | 10021 | United States |
| Investigational Site Number 840006 | Houston | Texas | 77030 | United States |
| Investigational Site Number 840008 | Seattle | Washington | 98105 | United States |
| Investigational Site Number 124001 | Toronto | M5G 1X8 | Canada |
Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| FG002 | Phase 1: Cabazitaxel 30 mg/m^2 | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| FG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| FG004 | Phase 2: Cabazitaxel 30 mg/m^2 | Cabazitaxel at the MTD as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| COMPLETED |
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| NOT COMPLETED |
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| Phase 2 |
|
All treated (AT)/safety population was defined as all registered participants who actually received at least 1 dose or part of a dose of the investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1: Cabazitaxel 20 mg/m^2 | Cabazitaxel 20 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| BG001 | Phase 1: Cabazitaxel 25 mg/m^2 | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| BG002 | Phase 1: Cabazitaxel 30 mg/m^2 | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| BG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| BG004 | Phase 2: Cabazitaxel 30 mg/m^2 | Cabazitaxel at the maximum tolerated dose (MTD) as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number | participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1: Maximum Tolerated Dose of Cabazitaxel | MTD was highest dose level of cabazitaxel at which no more than 1 of 6 evaluable participants experienced dose limiting toxicities (DLT). DLT defined as an AE or abnormal laboratory values related to study treatment: hematologic DLTs: any Grade(G)4 hematologic toxicity except neutropenia G4 lasting≤7 days,G3 or 4 febrile neutropenia except G3 or 4 febrile neutropenia in absence of granulocyte-colony stimulating factor prophylaxis, G4 thrombocytopenia; non-hematologic DLTs:any G≥3 non-hematologic toxicity except G3 nausea or G3 or4 vomiting, G3 or4 diarrhea,G3 or4 dehydration,G3 fatigue lasting≤7 days, inadequately treated hypersensitivity reactions, elevated transaminases<10* upper limit of normal of ≤7 days, re-treatment delay of>2 weeks due to delayed recovery from toxicity related to study treatment to baseline G or≤ G1(except for alopecia) and platelet transfusion during Cycle1. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. | DLT evaluable population defined as a subset of participants in the Phase 1 part of the study from the AT population who received the first dose of cabazitaxel and had sufficient safety evaluations or experienced a DLT during Cycle 1. | Posted | Number | mg/m^2 | Cycle 1 (21 days) |
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| Primary | Phase 2: Percentage of Participants With Objective Response (OR) | OR in participants was defined as the participants with a Complete Response (CR) or Partial Response (PR) after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks. CR and PR were based on modified response assessment in neuro-oncology (RANO) criteria for participants with CNS tumors. CR was defined as disappearance of all target lesions. PR was defined as ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to the baseline measurement. | Efficacy evaluable population was subset of AT population with measurable disease with a baseline and at least one post-baseline tumor evaluation.Number of participants analyzed=participants with available data for this endpoint. | Posted | Number | percentage of participants | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
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| Primary | Phase 2: Duration of Response (DOR) | DOR defined as time (in days) from date of first response until date of first documented progressive disease (PD) or death (from any cause), whichever came first. If progression or death was not observed, participant was censored at the date of participant's last progression-free tumor assessment prior to study cut-off date. PD as per RANO criteria was defined as ≥ 25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc.) plus any increase in tumor cross-sectional area (or tumor volume). | Due to no objective responses in Stage 1 of Phase 2, the analysis of duration of response was not performed.Hence, the data is not reported. | Posted | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
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| Secondary | Phase 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. Treatment emergent adverse events (TEAEs) were defined as AEs that developed or worsened in grade or became serious during the on-treatment period which was defined as the period from the time of first dose of cabazitaxel until 30 days following the last administration of cabazitaxel. | Analysis was performed on safety population (AT population). | Posted | Number | participants | Baseline up to DP or death due to any cause (maximum duration: 112.1 weeks for Phase 1 and 12.1 weeks for Phase 2) |
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| Secondary | Phase 1: Number of Participants With Objective Response | OR in participants was defined as the participants with a CR or PR after 3 cycles of cabazitaxel treatment and maintained for at least 4 weeks as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and RANO criteria for CNS tumors. For solid tumors, as per RECIST 1.1, CR defined as disappearance of all target and non-target lesions (any pathological lymph nodes, must had reduction in short axis to <10 mm); PR defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. For CNS tumors, as per RANO criteria, CR defined as disappearance of all target and non-target lesions; PR defined as a ≥50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to baseline measurement. | Analysis was performed on efficacy evaluable population. Number of participants analyzed=participants with available data for this endpoint. | Posted | Number | participants | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 112.1 weeks) |
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| Secondary | Phase 1 and 2: Pharmacokinetics (PK) Parameter of Cabazitaxel: Area Under the Plasma Concentration (AUC) Versus Time Curve | Blood samples for PK parameters were collected at 5 minutes before end of infusion (EOI), 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | PK population (for both Phase 1 and Phase 2 parts of the study) included all participants who received treatment on Day 1 of Cycle 1 and had at least one post-dose PK sample. Number of participants analyzed=participants with available data for this endpoint. | Posted | Mean | Standard Deviation | ng.h/mL | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
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| Secondary | Phase 1 and 2: PK Parameter of Cabazitaxel: Total Plasma Clearance (CL) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Analysis was performed on PK population (for both Phase 1 and Phase 2 parts of the study). Number of participants analyzed=participants with available data for this endpoint. | Posted | Mean | Standard Deviation | L/h/m^2 | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
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| Secondary | Phase 1 and 2: PK Parameter of Cabazitaxel: Volume of Distribution at Steady State (Vss) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Analysis was performed on PK population (for both Phase 1 and Phase 2 parts of the study). Number of participants analyzed=participants with available data for this endpoint. | Posted | Mean | Standard Deviation | L/m^2 | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
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| Secondary | Phase 1 and 2: PK Parameter of Cabazitaxel: Maximum Plasma Concentration Observed (Cmax) | Blood samples for PK parameters were collected at 5 minutes before EOI, 10 minutes, 30 minutes, 3 hours, 7 hours and 71 hours after the EOI on Day 1 of Cycle 1. | Analysis was performed on PK population (for both Phase 1 and Phase 2 parts of the study). Number of participants analyzed=participants with available data for this endpoint. | Posted | Mean | Standard Deviation | ng/mL | Day 1 of Cycle 1: 5 minutes before EOI up to 71 hours after the EOI |
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| Secondary | Phase 2: Progression Free Survival (PFS) | The PFS was defined as the time (in months) from the date of first dose administration until the date of first documented PD or death (from any cause), whichever came first. If progression or death was not observed, the participant was censored at the date of the participant's last progression-free tumor assessment prior to the study cut-off date. PD as per RANO criteria was defined as ≥25% increase in the product of perpendicular diameters of any target lesion, taking as reference the smallest product observed since the start of treatment or the appearance of one or more new lesions, or worsening neurologic status not explained by causes unrelated to tumor progression (example, anticonvulsant or corticosteroid toxicity, electrolyte disturbances, sepsis, hyperglycemia, presumed post-therapy swelling etc) plus any increase in tumor cross-sectional area (or tumor volume). The analysis was performed by Kaplan-Meier method. | Analysis was performed on efficacy evaluable population. Number of participants analyzed=participants with available data for this endpoint. | Posted | Median | 95% Confidence Interval | months | Baseline, every 9 weeks until DP or death due to any cause (maximum duration: 12.1 weeks) |
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| Secondary | Phase 2: Overall Survival (OS) | OS was defined as the time (in months) from the date of first dose administration until the date of death (from any cause). If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive and the study cut-off date. The analysis was performed by Kaplan-Meier method. | Analysis was performed on efficacy evaluable population. Number of participants analyzed=participants with available data for this endpoint. | Posted | Median | 95% Confidence Interval | months | Baseline up to death or study cut-off (maximum duration: 12.1 weeks) |
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All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (112.1 weeks for Phase 1 and 12.1 weeks for Phase 2) regardless of seriousness or relationship to investigational product.
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during 'on treatment period' (time from first dose of study drug to last dose of study drug + 30 days). Analysis was performed on safety population.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1: Cabazitaxel 20 mg/m^2 | Cabazitaxel 20 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). | 4 | 6 | 6 | 6 | ||
| EG001 | Phase 1: Cabazitaxel 25 mg/m^2 | Cabazitaxel 25 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). | 1 | 3 | 3 | 3 | ||
| EG002 | Phase 1: Cabazitaxel 30 mg/m^2 | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). | 5 | 7 | 7 | 7 | ||
| EG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). | 3 | 7 | 7 | 7 | ||
| EG004 | Phase 2: Cabazitaxel 30 mg/m^2 | Cabazitaxel at the MTD as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). | 12 | 16 | 15 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Death | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Stoma site infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Varicella zoster virus infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Brain herniation | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Intracranial tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nerve root compression | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypoventilation | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDra 18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Eyelid pain | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Device occlusion | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Oedema | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Enterocolitis bacterial | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Lip infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Mucosal infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Varicella zoster virus infection | Infections and infestations | MedDra 18.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Rectal injury | Injury, poisoning and procedural complications | MedDra 18.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Candida test positive | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Coronavirus test positive | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDra 18.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDra 18.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Joint hyperextension | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra 18.1 | Systematic Assessment |
| |
| Accessory nerve disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cerebellar ataxia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cerebellar syndrome | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cranial nerve paralysis | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dysarthria | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Facial nerve disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypoglossal nerve disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypotonia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| VIIIth nerve lesion | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| VIth nerve disorder | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| VIth nerve paralysis | Nervous system disorders | MedDra 18.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Deja vu | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dysmenorrhoea | Reproductive system and breast disorders | MedDra 18.1 | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDra 18.1 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDra 18.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDra 18.1 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDra 18.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDra 18.1 | Systematic Assessment |
|
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact-US@sanofi.com |
| ID | Term |
|---|---|
| C552428 | cabazitaxel |
| C532412 | XRP6258 |
Not provided
Not provided
Not provided
| 5-6 years |
|
| 7-11 years |
|
| 12-18 years |
|
| Male |
|
|
|
| OG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| OG004 | Phase 2: Cabazitaxel 30 mg/m^2 | Cabazitaxel at the maximum tolerated dose (MTD) as determined in phase 1 (30 mg/m^2) IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| OG002 | Phase 1: Cabazitaxel 30 mg/m^2 | Cabazitaxel 30 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
| OG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| OG003 | Phase 1: Cabazitaxel 35 mg/m^2 | Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| OG003 |
| Phase 1: Cabazitaxel 35 mg/m^2 |
Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| OG003 |
| Phase 1: Cabazitaxel 35 mg/m^2 |
Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| OG003 |
| Phase 1: Cabazitaxel 35 mg/m^2 |
Cabazitaxel 35 mg/m^2 IV infusion on Day 1 of each 21-day cycle until DP or discontinuation due to AE or death (from any cause). |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|