A Dose Finding Study of XRP6258 in Patients With Advanced Solid Tumors
- To determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of XRP6258 when given as a weekly 1-hour intravenous (i.v.) infusion for the first 4 consecutive weeks of each 5-week treatment cycle (Day 1, Day 8, Day 15, Day 22 of each 5-week treatment cycle).
Secondary Objectives :
- To define the safety profile of the drug
- To establish the recommended dose and time interval for future Phase II trials
- To determine the pharmacokinetic (PK) profile of XRP6258 in man
- To assess the absolute oral bioavailability of XRP6258 at the i.v. recommended dose (following Protocol Amendment No. 2)
- To look for evidence of antitumor activity
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Finding Study of XRP6258 Administered as a Weekly 1-hour Intravenous Infusion to Patients With Advanced Solid Tumors|
- Dose-limiting toxicity [ Time Frame: Up to 35 months ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Time Frame: Up to 35 months ] [ Designated as safety issue: Yes ]
- Number of patients with adverse events [ Time Frame: Up to 35 months ] [ Designated as safety issue: Yes ]
- Antitumor activity [ Time Frame: Up to 35 months ] [ Designated as safety issue: No ]Measured by X-ray, ultrasound and/or scans
- Pharmacokinetic parameters including Cmax, AUC(0-t), AUC, t, t1/2λz (h), Vss, CL, accumulation ratio, Tmax metabolite ratio and F (bioavailability) [ Time Frame: Up to 35 months ] [ Designated as safety issue: No ]
|Study Start Date:||October 1999|
|Study Completion Date:||October 2002|
|Primary Completion Date:||August 2002 (Final data collection date for primary outcome measure)|
IV escalation part:
XRP6258 administered as a 1-hour IV infusion on Days 1, 8, 15 and 22 of each 5-week cycle until evidence of disease progression, unacceptable toxicity or patient's withdrawal.
Oral bioavailability part:
XRP6258 administered at the dose of 8.4 mg/m² as an oral administration on Day 1 Cycle 1 and as a weekly 1-hour i.v. infusion at the subsequent weeks of treatment. Patients receiving oral administration at Day 1, Cycle 1 are to fast for 12 hours before and 4 hours after administration.
Drug: Cabazitaxel (XRP6258)
Pharmaceutical form: infusion solution Route of administration: Intravenous
Other Name: Jevtana
The duration of the study will include the following periods:
- Pretreatment: 28 to 7 days before first infusion
- Treatment: Weekly for the first four consecutive weeks during 5-week treatment cycle
- Post-treatment: 3 - 4 weeks after last infusion.
Treatment may be continued until disease progression or unacceptable toxicity or patient refusal.