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

Neoplasm Malignant Clinical Trial

Official title:

Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01140607
• Other study ID #: POP6792
• Secondary ID: U1111-1116-5845
• Status: Completed
• Phase: Phase 1
• First received: May 28, 2010
• Last updated: July 20, 2015
• Start date: May 2010
• Est. completion date: July 2014

Study information

• Verified date: July 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Malignant
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Investigational Site Number 840019	Baltimore	Maryland
United States	Investigational Site Number 840010	Bethlehem	Pennsylvania
United States	Investigational Site Number 840012	Boston	Massachusetts
United States	Investigational Site Number 840021	Canton	Ohio
United States	Investigational Site Number 840007	Cincinnati	Ohio
United States	Investigational Site Number 840017	Decatur	Illinois
United States	Investigational Site Number 840016	Jacksonville	Florida
United States	Investigational Site Number 840014	La Jolla	California
United States	Investigational Site Number 840013	Loma Linda	California
United States	Investigational Site Number 840003	Metairie	Louisiana
United States	Investigational Site Number 840006	San Antonio	Texas
United States	Investigational Site Number 840001	St Louis	Missouri
United States	Investigational Site Number 840002	Tampa	Florida
United States	Investigational Site Number 840020	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLT)	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.	cycle 1 (3 weeks)	Yes
Secondary	Safety investigations (physical examination, vital signs and laboratory tests)	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	up to 30 days after the last dosing	Yes
Secondary	Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration		cycle 1 (3 weeks)	No
Secondary	Cabazitaxel effect on CYP3A enzyme activity		single dosing on day -1 and day 1	No