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

NCT01755390 | Completed Phase 1

• 1 other identifier: TED6189
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 2

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

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity

  Up to 35 months

• Maximum tolerated dose

  Up to 35 months

Secondary Outcomes (3)

• Number of patients with adverse events

  Up to 35 months

• Antitumor activity

  Up to 35 months

• 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

Study Arms (1)

Cabazitaxel

EXPERIMENTAL

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)

Interventions

Cabazitaxel (XRP6258) DRUG

Pharmaceutical form: infusion solution Route of administration: Intravenous

Also known as: Jevtana

Cabazitaxel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to beginning protocol specific procedures
• Histologically proven cancer at the first diagnosis. At study entry, it was desirable but not required to have histological or cytological proof of metastasis in the case of a 1 single metastatic target lesion.
• Advanced neoplastic disease that was refractory to conventional treatment or for which no standard therapy existed
• Progressive disease
• Age 18-70 years
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 to 2
• Off previous anticancer (radio- or chemo-) therapy for at least 4 weeks and 6 weeks if prior nitrosoureas, mitomycin C; recovery from the toxic effects of prior treatment (Grade ≤1, except alopecia any grade)
• Off previous immunotherapy for at least 1 week provided that patients did not have any residual signs of any toxicity
• Adequate organ function including: neutrophils ≥2.0 × 109/L; platelets ≥100 × 109/L, creatinine \<120 μmol/L (if borderline creatinine values, the creatinine clearance had to be ≥60 mL/min); total bilirubin within normal limit; alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/alkaline phosphatase (ALP) ≤2.5-fold the upper normal limits of the institutional norms (ALP ≤2.5 UNL)
• Patients registered in this trial had to be treated and followed at the participating centers
• Patients who had received previous treatment with paclitaxel or docetaxel could be included provided that they did not have any residual signs of taxane toxicity (except alopecia any grade and peripheral neuropathy Grade 1)

You may not qualify if:

• Hematological malignancies
• Pregnant or lactating women or women of childbearing potential (eg, not using adequate contraception)
• Symptomatic brain metastases
• Previous extensive radiotherapy (\>20% of bone marrow area)
• 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.
• 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
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to patient registration
• Concurrent treatment with any other anticancer therapy
• Concomitant radiotherapy
• 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.
• More than 2 prior chemotherapy regimens containing mitomycin C or nitrosoureas

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Sanofi

Paris, France

Location

Sanofi

Barcelona, Spain

Location

Related Publications (1)

• Fumoleau P, Trigo JM, Isambert N, Semiond D, Gupta S, Campone M. Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours. BMC Cancer. 2013 Oct 7;13:460. doi: 10.1186/1471-2407-13-460.

  PMID: 24099585 DERIVED

MeSH Terms

Interventions

cabazitaxel; XRP6258

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: December 24, 2012
• Study Start: October 1, 1999
• Primary Completion: August 1, 2002
• Study Completion: October 1, 2002
• Last Updated: December 24, 2012

Record last verified: 2012-12

Locations

FR (1); ES (1)