A Dose Finding Study of XRP6258 in Patients With Advanced Solid Tumors

Phase 1

Completed

• Conditions: Advanced Solid Tumor
• Interventions: Drug: Cabazitaxel (XRP6258)

• Registration Number: NCT01755390
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

- 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

Detailed Description

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.

Study Timeline

• Study Start: 1999-10
• Primary Completion: 2002-08
• Study Completion: 2002-10
• Status Verified: 2012-12
• Study First Submitted: 2012-12-17
• Study First Submitted QC: 2012-12-21
• Last Update Submitted: 2012-12-21
• Study First Posted: 2012-12-24
• Last Update Posted: 2012-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

1. Hematological malignancies

2. Pregnant or lactating women or women of childbearing potential (eg, not using adequate contraception)

3. Symptomatic brain metastases

4. Previous extensive radiotherapy (>20% of bone marrow area)

5. Current peripheral neuropathy of any origin including significant residual symptoms due to the use of eg, vinca-alkaloids or platinum ≥Grade 2 according to the National Cancer Institute common terminology criteria for adverse events.

6. Other serious illness or medical conditions:

   • Congestive heart failure or angina pectoris even if medically controlled, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or arrhythmias
   • Existence of significant neurological or psychiatric disorders including dementia or seizures
   • Active infection
   • Uncontrolled peptic ulcer, unstable diabetes mellitus, or other contraindications for the use of corticosteroids

7. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to patient registration

8. Concurrent treatment with any other anticancer therapy

9. Concomitant radiotherapy

10. Concomitant treatment with corticosteroids. However, patients receiving chronic treatment with corticosteroids (≤20 mg of methylprednisolone or ≤4 mg of dexamethasone or equivalent dose of other corticosteroids), for whatever reason, were eligible.

11. More than 2 prior chemotherapy regimens containing mitomycin C or nitrosoureas

12. More than 2 prior chemotherapy regimens for advanced disease

13. Prior history of severe allergic reaction to docetaxel or paclitaxel

14. Prior intensive chemotherapy with autologous stem cell rescue

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cabazitaxel	Cabazitaxel (XRP6258)	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.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity	Up to 35 months
Maximum tolerated dose	Up to 35 months

Secondary Outcome Measures

Name	Time	Method
Number of patients with adverse events	Up to 35 months
Antitumor activity	Up to 35 months	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)	Up to 35 months

Trial Locations

Locations (1)

Sanofi; 🇪🇸 Barcelona, Spain