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Maximum tolerated dose not able to be determined
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Primary Objectives:
Secondary Objectives:
For study part 1, dose levels were to be escalated according to predefined dose escalation decision rules. The Maximum Administered Dose (MAD) was reached at the dose level when at least 2 patients developed a DLT during the first 3 weeks of treatment. There was no further dose escalation when this dose was achieved. The MTD was defined as the highest dose at which 0 or 1 of 3 to 6 patients, respectively, experienced DLT during the first 3 weeks of treatment.
The study consisted of a screening phase (maximum length of 21-day), a treatment phase with 21-day treatment cycles and a 30-day follow-up visit after the last dose of study medication.
The cut-off date for study part 1 was when last participant completed the first treatment cycle and the subsequent 30 days follow-up.
The cut off date for study part 2 was when all participants experienced disease progression, unacceptable toxicity, consent withdrawal or the last participant had completed 26 weeks or 6 cycles on study treatment, whichever came first.
Participants could continue to be treated on study as long as they were benefiting from study treatment and had not met study withdrawal criteria. After withdrawal from study treatment, further treatment, if any, was at the discretion of the Investigator.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cabazitaxel + gemcitabine | Experimental | Cabazitaxel and gemcitabine on Day 1 then gemcitabine alone on Day 8 every 3 weeks until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision. On Day 1, cabazitaxel was given either first followed by gemcitabine (part 1a) or after gemcitabine with 1 hour gap between the two infusions (part 1b). Required premedication with antihistamine, corticosteroid and H2 antagonist was administered intravenously 30 minutes before each dose of cabazitaxel. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cabazitaxel | Drug | Pharmaceutical form: 60 mg/1.5 ml concentrate solution for infusion Route of administration: Intravenous infusion over 60 minutes Dosage:
|
| Measure | Description | Time Frame |
|---|---|---|
| Participants With Dose Limiting Toxicities During Dose Escalation | Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4). | Day 1 to Day 21 of the first treatment cycle |
| Objective Response Rate With MTD | Objective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion. The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed. | Fron Day 1 up to a maximum of 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Time To Progression With MTD | Time to progression (TTP) was defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression (>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions). Median TTP was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed. |
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Inclusion criteria:
Exclusion criteria:
The above information is not intended to contain all considerations relevant to a patient'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 840002 | Detroit | Michigan | 48201 | United States | ||
| Investigational Site Number 840005 |
At each dose level, there was a 1-week gap between the treatment of the first participant and the next 2 participants to evaluate toxicity.
Before escalating to the next dose level, at least 3 participants were to be evaluable for the criteria defining dose limiting toxicity (DLT).
Participants were enrolled in 4 sites in the United States. Since it was not possible to determine the maximum Tolerated Dose (MTD) in study part 1, no participant was enrolled in study part 2 and the study was stopped.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1: Cabazitaxel + Gemcitabine Dose Level 0 | Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| FG001 | Part 1: Cabazitaxel + Gemcitabine Dose Level -1 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| FG002 | Part 1: Cabazitaxel + Gemcitabine Dose Level -2 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| FG003 | Part 1: Gemcitabine + Cabazitaxel Dose Level 0 | gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| FG004 | Part 2: Cabazitaxel + Gemcitabine MTD | Cabazitaxel IV and gemcitabine IV on Day 1 then, gemcitabine IV on Day 8 at the Maximum Tolerated Dose (MTD) as determined in study part 1 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1: Cabazitaxel + Gemcitabine Dose Level 0 | Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| 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 | Participants With Dose Limiting Toxicities During Dose Escalation | Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4). | DLT population: All participants who completed assessments for DLT evaluation for Cycle 1 and either:
| Posted | Number | participants | Day 1 to Day 21 of the first treatment cycle |
|
from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cabazitaxel + Gemcitabine Dose Level 0 | Cabazitaxel 20 mg/m^2 IV followed by gemcitabine 1000 mg/m^2 IV on Day 1 then, gemcitabine 1000 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchiolitis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
Pharmacokinetic results need to be confirmed due to the limited data available.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | sanofi-aventis | Contact-US@sanofi.com |
Not provided
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C552428 | cabazitaxel |
| C532412 | XRP6258 |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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|
|
| gemcitabine | Drug | Pharmaceutical form: According to United States Package Insert (USPI) Route of administration: Intravenous infusion over 30 minutes Dosage:
|
|
|
| Fron Day 1 up to a maximum of 12 months |
| Duration of Response With MTD | Duration of Response (DR) was defined as the time from the first documentation of RECIST-defined objective tumor response to the first documentation of RECIST-defined objective tumor progression or death. Median DR was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed. | Fron Day 1 up to a maximum of 12 months |
| Participants With Adverse Events | Summary of participants with adverse events (AEs) according to severity and relationship to study drug as assessed by the investigator. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used to grade the severity of AE. Treatment-emergent adverse events (TEAEs) are AEs that occurred or worsened from start of treatment up to 30 days after treatment ceased. NCI CTCAE v.3.0 grade 3 =severe and grade 4= life-threatening or disabling. | from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks) |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples for cabazitaxel assay were collected during cycle 1 and cabazitaxel plasma concentrations were determined using a validated liquid chromatography with tandem mass spectometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1 ng/mL. Pharmacokinetic (PK) parameters were calculated from plasma concentrations using non-compartmental analysis. | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to the last measurable concentration at time t. | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC) | Area under the plasma concentration versus time curve extrapolated to infinity | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples for gemcitabine assay were collected on Day 1 of cycle 1 at the following timepoints:
Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax) | Blood samples for gemcitabine assay were collected on Day 8 of cycle 1 at the following timepoints:
Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax) | Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
| Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC | Ratio Day 1/Day 8 for AUClast and AUC were calculated to assess the effect of cabazitaxel on gemcitabine exposure. | Day 1 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) and Day 8 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) |
| Cincinnati |
| Ohio |
| 45267-0542 |
| United States |
| Investigational Site Number 840004 | Philadelphia | Pennsylvania | 19111 | United States |
| Investigational Site Number 840001 | Nashville | Tennessee | 37232 | United States |
| Disease progression |
|
| Other |
|
| Not treated; protocol exclusion |
|
| Part 1: Cabazitaxel + Gemcitabine Dose Level -1 |
Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| BG002 | Part 1: Cabazitaxel + Gemcitabine Dose Level -2 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| BG003 | Part 1: Gemcitabine + Cabazitaxel Dose Level 0 | Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Body Surface Area | Mean | Standard Deviation | m^2 |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG criteria:
| Number | participants |
|
| Primary Tumor Site | Number | participants |
|
| Histological Type | Number | participants |
|
| Stage at Diagnosis | Cancer staging is on a scale of I-IV with higher numbers indicating an increase in progression of the disease. Stage I: cancers are localized to one part of the body. Stage II: cancers are early locally advanced. Stage III: cancers are late locally advanced. Stage IV: cancers have often metastasized, or spread to other organs or throughout the body. | Number | participants |
|
| Number of Organs Involved | Mean | Standard Deviation | organs |
|
| OG001 | Cabazitaxel + Gemcitabine Dose Level -1 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| OG002 | Cabazitaxel + Gemcitabine Dose Level -2 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
| OG003 | Gemcitabine + Cabazitaxel Dose Level 0 | Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision |
|
|
| Secondary | Time To Progression With MTD | Time to progression (TTP) was defined as the time from first treatment administration to first documentation of RECIST-defined objective tumor progression (>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions). Median TTP was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed. | Posted | Fron Day 1 up to a maximum of 12 months |
|
|
| Secondary | Duration of Response With MTD | Duration of Response (DR) was defined as the time from the first documentation of RECIST-defined objective tumor response to the first documentation of RECIST-defined objective tumor progression or death. Median DR was to be estimated using the Kaplan-Meier method. Due to the inability to determine MTD during the study part 1, the analysis was not performed. | Posted | Fron Day 1 up to a maximum of 12 months |
|
|
| Secondary | Participants With Adverse Events | Summary of participants with adverse events (AEs) according to severity and relationship to study drug as assessed by the investigator. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used to grade the severity of AE. Treatment-emergent adverse events (TEAEs) are AEs that occurred or worsened from start of treatment up to 30 days after treatment ceased. NCI CTCAE v.3.0 grade 3 =severe and grade 4= life-threatening or disabling. | all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment | Posted | Number | participants | from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks) |
|
|
|
| Post-Hoc | Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 | Participant Best response was assessed by investigator using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1:
| all treated (AT) population: All enrolled participants who received at least 1 part of a dose of study treatment. | Posted | Number | participants | Up to a maximum of 22 cycles (median 4 cycles) |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples for cabazitaxel assay were collected during cycle 1 and cabazitaxel plasma concentrations were determined using a validated liquid chromatography with tandem mass spectometry (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1 ng/mL. Pharmacokinetic (PK) parameters were calculated from plasma concentrations using non-compartmental analysis. | PK population: All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample, and with no prohibited concomitant medications | Posted | Mean | Standard Deviation | ng/ml | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax) | PK population as previously defined | Posted | Median | Full Range | hours (hr) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to the last measurable concentration at time t. | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC) | Area under the plasma concentration versus time curve extrapolated to infinity | PK population as previously defined. Six participants' assays could not be used for AUC. | Posted | Mean | Standard Deviation | ng*hr/ml | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z) | PK population as previously defined | Posted | Mean | Standard Deviation | hours (hr) | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL) | PK population as previously defined. Six participants' assays could not be used for CL. | Posted | Mean | Standard Deviation | L/hr | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss) | PK population as previously defined. One participant's assay could not be used for Vss. | Posted | Mean | Standard Deviation | L | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | PK population as previously defined. Six participants' assays could not be used for CL/BSA. | Posted | Mean | Standard Deviation | L/hr/m^2 | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | PK population as previously defined. One participant's assays could not be used for Vss/BSA. | Posted | Mean | Standard Deviation | L/m^2 | before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples for gemcitabine assay were collected on Day 1 of cycle 1 at the following timepoints:
Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | PK population as previously defined. | Posted | Mean | Standard Deviation | ng/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax) | PK population as previously defined | Posted | Median | Full Range | hours (hr) | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | hours | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/hr | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/hr/m^2 | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | PK population as previously defined. Five participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/m^2 | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax) | Blood samples for gemcitabine assay were collected on Day 8 of cycle 1 at the following timepoints:
Gemcitabine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | PK population as previously defined | Posted | Mean | Standard Deviation | ng/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax) | PK population as previously defined | Posted | Median | Full Range | hours (hr) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | hours (hr) | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/hr | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/hr/m^2 | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | L/m^2 | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax) | Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | PK population as previously defined | Posted | Mean | Standard Deviation | ng/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax) | PK population as previously defined | Posted | Median | Full Range | hours | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z) | PK population as previously defined | Posted | Mean | Standard Deviation | hours | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC) | PK population as previously defined. Two participants' assays could not be used in the analysis. | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 1 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax) | Blood samples collected for gemcitabine assay were used to assay gemcitabine metabolite, 2',2' difluorodeoxyuridine(dFdU). 2',2' difluorodeoxyuridine plasma concentrations were determined using validated LC-MS/MS methods with a LLOQ of 50 ng/mL. PK parameters were calculated from plasma concentrations using non-compartmental analysis. | All enrolled participants who received at least 1 part of a dose of study treatment and had at least 1 post treatment analyzable PK sample and with no prohibited concomitant medications. | Posted | Mean | Standard Deviation | ng/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax) | PK population as previously defined | Posted | Median | Full Range | hours | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast) | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z) | PK population as previously defined | Posted | Mean | Standard Deviation | hours | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC) | PK population as previously defined | Posted | Mean | Standard Deviation | ng*hr/ml | 7 to 9 timepoints from start of Day 8 infusion up to 24h hours after the end of infusion depending on the sequence of treatment on Day 1 |
|
|
|
| Secondary | Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC | Ratio Day 1/Day 8 for AUClast and AUC were calculated to assess the effect of cabazitaxel on gemcitabine exposure. | Enrolled participants who received at least 1 part of a dose of study treatment and had valid Day 1 and Day 8 PK samples. Valid PK samples included at least 1 post treatment analyzable PK sample and no prohibited concomitant medications. | Posted | Mean | Full Range | ratio | Day 1 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) and Day 8 (7 to 9 timepoints from start of infusion up to 24h hours after the end of infusion) |
|
|
|
| Primary | Objective Response Rate With MTD | Objective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion. The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed. | Posted | Fron Day 1 up to a maximum of 12 months |
|
|
| 5 |
| 5 |
| 5 |
| 5 |
| EG001 | Cabazitaxel + Gemcitabine Dose Level -1 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 900 mg/m^2 IV on Day 1 then, gemcitabine 900 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision | 2 | 5 | 5 | 5 |
| EG002 | Cabazitaxel + Gemcitabine Dose Level -2 | Cabazitaxel 15 mg/m^2 IV followed by gemcitabine 700 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision | 2 | 2 | 2 | 2 |
| EG003 | Gemcitabine + Cabazitaxel Dose Level 0 | Gemcitabine 700 mg/m^2 IV followed by cabazitaxel 15 mg/m^2 IV on Day 1 then, gemcitabine 700 mg/m^2 IV on Day 8 21-day treatment cycles until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision | 4 | 6 | 6 | 6 |
| Pneumonia | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA (14.1) | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Intestinal dilatation | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Blood electrolytes abnormal | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (14.1) | Systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Normochromic normocytic anaemia | Blood and lymphatic system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abnormal dreams | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (14.1) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA (14.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Arthalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (14.1) | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA (14.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Catheter site haematoma | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Early satiety | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Generalized oedema | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Musosal inflammation | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (14.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Blood alkalne phosphatase increased | Investigations | MedDRA (14.1) | Systematic Assessment |
|
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
| Anastomotic ulcer | Injury, poisoning and procedural complications | MedDRA (14.1) | Systematic Assessment |
|
At least 45 days in advance of proposed submission, the Investigator should forward a copy of the manuscript or abstract for review by the sponsor, and, if necessary, delay publication or communication for a limited time in order to protect the confidentiality or proprietary nature of any information contained therein.
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Any TEAE |
|
| - Drug-related TEAE |
|
| Grade 3-4 TEAE |
|
| - Grade 3-4 drug-related TEAE |
|
| Serious TEAE |
|
| - Drug-related serious TEAE |
|
| AE leading to drug withdrawn |
|
| - Drug-related AE leading to drug withdrawn |
|
| AE leading to death |
|
| AE leading to dose reduction |
|
| AE leading to dose delay |
|
| Partial response |
|
| Stable disease |
|
| Progressive disease |
|
| Not evaluable |
|
| AUC |
|