Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor

This study has been terminated.
(Maximum tolerated dose not able to be determined)
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01001221
First received: October 23, 2009
Last updated: September 9, 2013
Last verified: September 2013
Results First Received: May 20, 2013  
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms, Malignant
Interventions: Drug: cabazitaxel
Drug: gemcitabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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).


Reporting Groups
  Description
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

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

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

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

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


Participant Flow:   Overall Study
    Part 1: Cabazitaxel + Gemcitabine Dose Level 0     Part 1: Cabazitaxel + Gemcitabine Dose Level -1     Part 1: Cabazitaxel + Gemcitabine Dose Level -2     Part 1: Gemcitabine + Cabazitaxel Dose Level 0     Part 2: Cabazitaxel + Gemcitabine MTD  
STARTED     5     5     3     6     0 [1]
Treated     5     5     2     6     0  
Completed 1st Treatment Cycle     5     5     2     6     0  
COMPLETED     0 [2]   0 [2]   0 [2]   0 [2]   0  
NOT COMPLETED     5     5     3     6     0  
Adverse Event                 1                 2                 0                 2                 0  
Disease progression                 3                 2                 2                 4                 0  
Not specified                 1                 1                 0                 0                 0  
Not treated; protocol exclusion                 0                 0                 1                 0                 0  
[1] Inability to determine the MTD during study part 1
[2] Participants treated until disease progression or unacceptable toxicity.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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

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

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

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

Total Total of all reporting groups

Baseline Measures
    Part 1: Cabazitaxel + Gemcitabine Dose Level 0     Part 1: Cabazitaxel + Gemcitabine Dose Level -1     Part 1: Cabazitaxel + Gemcitabine Dose Level -2     Part 1: Gemcitabine + Cabazitaxel Dose Level 0     Total  
Number of Participants  
[units: participants]
  5     5     3     6     19  
Age  
[units: years]
Mean ± Standard Deviation
  60.8  ± 6.6     59.2  ± 9.2     53.0  ± 14.8     56.3  ± 16.1     57.7  ± 11.5  
Gender  
[units: participants]
         
Female     2     2     1     3     8  
Male     3     3     2     3     11  
Race/Ethnicity, Customized  
[units: participants]
         
Asian/Oriental     0     0     1     0     1  
Black     0     1     0     0     1  
Caucasian/White     4     4     2     6     16  
Other     1     0     0     0     1  
Body Surface Area  
[units: m^2]
Mean ± Standard Deviation
  1.87  ± 0.32     1.82  ± 0.21     1.98  ± 0.42     1.84  ± 0.12     1.87  ± 0.24  
Eastern Cooperative Oncology Group (ECOG) Performance Status [1]
[units: participants]
         
0     0     2     1     1     4  
1     5     3     2     5     15  
2     0     0     0     0     0  
Primary Tumor Site  
[units: participants]
         
Bladder     0     0     1     1     2  
Colon     0     1     0     0     1  
Head/neck     0     1     1     0     2  
Lung     2     1     1     0     4  
Muscle/soft tissue     0     0     0     1     1  
Other     0     1     0     0     1  
Ovaries     0     0     0     1     1  
Pancreas     1     1     0     1     3  
Pelvis     0     0     0     1     1  
Prostate     2     0     0     0     2  
Skin     0     0     0     1     1  
Histological Type  
[units: participants]
         
Adenocarcinoma     2     4     0     2     8  
Squamous cell carcinoma     0     1     0     0     1  
Other     3     0     3     4     10  
Stage at Diagnosis [2]
[units: participants]
         
Stage I     0     0     0     0     0  
Stage II     0     1     0     0     1  
Stage III     0     3     0     1     4  
Stage IV     5     0     0     2     7  
Unknown     0     1     3     3     7  
Number of Organs Involved  
[units: organs]
Mean ± Standard Deviation
  4.0  ± 1.6     2.6  ± 0.5     3.3  ± 0.6     2.0  ± 0.6     2.9  ± 1.2  
[1]

ECOG criteria:

  • 0: Fully active
  • 1: Ambulatory, carry out work of a light or sedentary nature
  • 2: Ambulatory, capable of all selfcare
  • 3: Capable of limited selfcare, confined to bed or chair more than 50% of waking hours
  • 4: Completely disabled, no selfcare, totally confined to bed or chair
  • 5: Dead
[2]

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.




  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Participants With Dose Limiting Toxicities During Dose Escalation   [ Time Frame: Day 1 to Day 21 of the first treatment cycle ]

2.  Primary:   Objective Response Rate With MTD   [ Time Frame: Fron Day 1 up to a maximum of 12 months ]

3.  Secondary:   Time To Progression With MTD   [ Time Frame: Fron Day 1 up to a maximum of 12 months ]

4.  Secondary:   Duration of Response With MTD   [ Time Frame: Fron Day 1 up to a maximum of 12 months ]

5.  Secondary:   Participants With Adverse Events   [ Time Frame: from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks) ]

6.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax)   [ Time Frame: 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 ]

7.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax)   [ Time Frame: 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 ]

8.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)   [ Time Frame: 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 ]

9.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Area Under the Time Concentration Curve (AUC)   [ Time Frame: 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 ]

10.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Terminal Half-life (t1/2z)   [ Time Frame: 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 ]

11.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance (CL)   [ Time Frame: 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 ]

12.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State (Vss)   [ Time Frame: 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 ]

13.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)   [ Time Frame: 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 ]

14.  Secondary:   Pharmacokinetic of Cabazitaxel on Cycle 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)   [ Time Frame: 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 ]

15.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)   [ Time Frame: 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 ]

16.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)   [ Time Frame: 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 ]

17.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)   [ Time Frame: 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 ]

18.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)   [ Time Frame: 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 ]

19.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Terminal Half-life (t1/2z)   [ Time Frame: 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 ]

20.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance (CL)   [ Time Frame: 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 ]

21.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State (Vss)   [ Time Frame: 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 ]

22.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)   [ Time Frame: 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 ]

23.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 1: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)   [ Time Frame: 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 ]

24.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)   [ Time Frame: 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 ]

25.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)   [ Time Frame: 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 ]

26.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve From Time 0 To the Real Time Tlast (AUClast)   [ Time Frame: 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 ]

27.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Terminal Half-life (t1/2z)   [ Time Frame: 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 ]

28.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)   [ Time Frame: 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 ]

29.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance (CL)   [ Time Frame: 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 ]

30.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State (Vss)   [ Time Frame: 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 ]

31.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Total Plasma Clearance Normalized to Body Surface Area (CL/BSA)   [ Time Frame: 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 ]

32.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1 Day 8: Volume of Distribution at Steady State Normalized to Body Surface Area (Vss/BSA)   [ Time Frame: 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 ]

33.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Maximum Plasma Concentration Observed (Cmax)   [ Time Frame: 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 ]

34.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Time to Maximum Concentration (Tmax)   [ Time Frame: 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 ]

35.  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)   [ Time Frame: 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 ]

36.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Terminal Half-life (t1/2z)   [ Time Frame: 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 ]

37.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 1: Area Under the Time Concentration Curve (AUC)   [ Time Frame: 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 ]

38.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Maximum Plasma Concentration Observed (Cmax)   [ Time Frame: 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 ]

39.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Time to Maximum Concentration (Tmax)   [ Time Frame: 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 ]

40.  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)   [ Time Frame: 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 ]

41.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Terminal Half-life (t1/2z)   [ Time Frame: 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 ]

42.  Secondary:   Pharmacokinetic of 2',2' Difluorodeoxyuridine on Cycle 1 Day 8: Area Under the Time Concentration Curve (AUC)   [ Time Frame: 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 ]

43.  Secondary:   Pharmacokinetic of Gemcitabine on Cycle 1: Ratio Day 1/Day 8 for AUClast and AUC   [ Time Frame: 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) ]

44.  Post-Hoc:   Participant Best Response as Per the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1   [ Time Frame: Up to a maximum of 22 cycles (median 4 cycles) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Pharmacokinetic results need to be confirmed due to the limited data available.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact-US@sanofi.com


No publications provided


Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01001221     History of Changes
Other Study ID Numbers: TCD11068
Study First Received: October 23, 2009
Results First Received: May 20, 2013
Last Updated: September 9, 2013
Health Authority: United States: Food and Drug Administration