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Safety and Pharmacokinetic Study of Cabazitaxel in Patients With Advanced Solid Tumors and Liver Impairment

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT01140607
Collaborator
(none)
56
Enrollment
14
Locations
5
Arms
50
Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objectives:

  • To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment

  • To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment

  • To correlate PK variables with pharmacodynamic (PD) safety parameters in order to guide prescribers with regard to dosing in this patient population

  • To assess the effect of cabazitaxel at recommended dose of 25mg/m^2 on CYP3A enzyme activity using midazolam as probe in an additional cohort of cancer patients with normal hepatic function.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cabazitaxel (XRP6258)
 Phase 1

Detailed Description

The study consists of:

  • a screening phase (maximum length of 21-day).

  • a treatment phase with 21-day study treatment cycles. Cycle lengths may be extended up to maximum of 12 additional days in case of unresolved toxicity.

Patients continue to receive treatment until they experience, unacceptable toxicities/AEs, disease progression ,withdraw their consent, or the investigator decides to discontinue the patient, or study cut-off, whichever comes first.

  • a 30-day follow-up visit after the last dose of study medication.

The cut off date is when the last patient treated has completed cycle 1 and the subsequent 30 days follow-up.

Patients may continue to be treated as long as they are benefiting from study treatment and have not met study withdrawal criteria.

Study Design

Study Type:
Interventional
Actual Enrollment :
56 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment
Study Start Date :
May 1, 2010
Actual Primary Completion Date :
Jul 1, 2014
Actual Study Completion Date :
Jul 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1: normal hepatic function: cabazitaxel

cabazitaxel 25mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)
Pharmaceutical form:solution for infusion Route of administration: intravenous
Experimental: Cohort 2: mild hepatic impairment : cabazitaxel

cabazitaxel 20mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)
Pharmaceutical form:solution for infusion Route of administration: intravenous
Experimental: Cohort 3: moderate hepatic impairment: cabazitaxel

cabazitaxel 10mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)
Pharmaceutical form:solution for infusion Route of administration: intravenous
Experimental: Cohort 4: severe hepatic impairment: cabazitaxel

cabazitaxel 5 mg/m^2 or 10mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)
Pharmaceutical form:solution for infusion Route of administration: intravenous
Experimental: Cohort 5: normal hepatic function: cabazitaxel and midazolam

cabazitaxel 25mg/m^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Midazolam is given orally in single dosing on day -1 and day 1 (crossover)

Drug: Cabazitaxel (XRP6258)
Pharmaceutical form:solution for infusion Route of administration: intravenous

Outcome Measures

Primary Outcome Measures

  1. Incidence of Dose Limiting Toxicities (DLT) [cycle 1 (3 weeks)]

    A clinical adverse event or a laboratory abnormality is defined as DLT when it is drug-related as assessed by the investigator and agreed upon by the study committee.

Secondary Outcome Measures

  1. Safety investigations (physical examination, vital signs and laboratory tests) [up to 30 days after the last dosing]

    Physical examination includes Eastern Cooperative Oncology Group (ECOG) performance status and signs and symptoms. Vital signs includes weight, temperature, blood pressure and heart rate. Laboratory tests includes hematology, coagulation, biochemistry and urinalysis. Laboratory abnormalities are graded according to the NCI CTCAE v.4.0

  2. Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration [cycle 1 (3 weeks)]

  3. Cabazitaxel effect on CYP3A enzyme activity [single dosing on day -1 and day 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
  • Patients with a diagnosis of advanced, measurable or non-measurable, non-hematological cancer who have varying degrees of hepatic impairment. The cancer must be one that is either refractory to standard therapy or for which no standard therapy exists.
Exclusion criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2

  • Life expectancy <3 months

  • Need for a major surgical procedure or radiation therapy during the study

  • Evidence of another active malignancy

  • Prior chemotherapy, other investigational drug, biological therapy, targeted non-cytotoxic therapy and radiotherapy within 3 weeks prior to registration

  • Patients with known history of Gilbert's syndrome

  • Prior treatment with Cabazitaxel and a history of severe (Grade ≥3) hypersensitivity to taxanes, polysorbate-80, or to compounds with similar chemical structures

  • Prior history of bone marrow transplant

  • Any treatment known to induce CYP isoenzymes or to inhibit CYP3A4 activities within 2 weeks before or during the test period of the pharmacokinetic sampling. Moderate inhibitors within one week prior and during the pharmacokinetic sampling.

  • Any contra-indications to midazolam, according to the applicable labeling.

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Investigational Site Number 840014 La Jolla California United States 92093
2 Investigational Site Number 840013 Loma Linda California United States 92354
3 Investigational Site Number 840020 Washington District of Columbia United States 20037
4 Investigational Site Number 840016 Jacksonville Florida United States 32207
5 Investigational Site Number 840002 Tampa Florida United States 33612
6 Investigational Site Number 840017 Decatur Illinois United States 62526
7 Investigational Site Number 840003 Metairie Louisiana United States 70006
8 Investigational Site Number 840019 Baltimore Maryland United States 21201
9 Investigational Site Number 840012 Boston Massachusetts United States 02115
10 Investigational Site Number 840001 St Louis Missouri United States 63110
11 Investigational Site Number 840021 Canton Ohio United States 44718
12 Investigational Site Number 840007 Cincinnati Ohio United States 45267-0542
13 Investigational Site Number 840010 Bethlehem Pennsylvania United States 18015
14 Investigational Site Number 840006 San Antonio Texas United States 78229

Sponsors and Collaborators

  • Sanofi

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT01140607
Other Study ID Numbers:
  • POP6792
  • U1111-1116-5845
First Posted:
Jun 9, 2010
Last Update Posted:
Jul 21, 2015
Last Verified:
Jul 1, 2015
Additional relevant MeSH terms:
Neoplasms

Study Results

No Results Posted as of Jul 21, 2015