Clinical trial NCT00925743: A Study to Evaluate the Effects of Combining Cabazitaxel With Cisplatin Given Every 3 Weeks in Patients With Advanced Solid Cancer
Official title: A Dose-Escalation Study Of The Safety, Tolerability, And Pharmacokinetics Of Cabazitaxel In Combination With Cisplatin Administered Every 3 Weeks In Subjects With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Cancer
Keywords: Phase 1
XRP6258
cisplatin
Antineoplastic Combined Chemotherapy Protocols
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-06-22
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed as a phase 1, multicenter, open-label, single arm, dose-escalation, study of Cabazitaxel in combination with cisplatin, to determine safety, pharmacokinetics (PK), and efficacy in solid tumors (parts 1 and 2) and single sequence, two-treatment, crossover studies to determine the effect of strong CYP3A4 inhibition and induction on the PK of Cabazitaxel in patients with solid tumors (part 3 and part 4, respectively).

There are 4 parts to the study:

Part 1: Determine the Dose Limiting Toxicities (DLT)'s and Maximum Tolerated Dose (MTD) based on safety.

Part 2: Determine the anti-tumor activity of the combination regimen at the Maximum Tolerated Dose (MTD) in an extended cohort of patients.

Part 3: Determine the effect of a strong CYP3A4 inhibitor (ketoconazole) on the pharmacokinetic (PK) of Cabazitaxel.

Part 4: Determine the effect of a strong CYP3A4 inducer (rifampin) on the pharmacokinetic (PK) of Cabazitaxel.

Detailed description: The total duration on the study per subject will be about 26 weeks broken down as follows:

* A maximum of 21-day screening phase,
* 21-days (+/- 2 weeks) study treatment cycles,
* 30-day follow-up visit after the last dose of study medication.
* Cut-off date for parts 1, 2, 3 and 4: when the last patient has completed 6 cycles (parts 1 and 2) or 2 cycles (parts 3 and 4) of treatment or discontinued study treatment (for disease progression, unacceptable toxicity, withdrawal of consent, or investigator's decision to withdraw), whichever comes first, in the corresponding part.

Patients still receiving treatment at the cut-off date may continue to receive treatment beyond the cut-off date at investigator's discretion if benefiting.

Eligibility criteria: Inclusion criteria:

* confirmed metastatic or unremovable advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist, but for which cisplatin based therapy is appropriate
* signed informed consent

Exclusion criteria

* limited physical functioning (as evaluated by the Eastern Cooperative Oncology Group (ECOG) scale)
* inability to follow study requirements and schedule
* treatment of cancer within 3 weeks of study, concurrent treatment in another clinical trial or with any other cancer therapy
* serious medical illness at same time of study and/or significantly abnormal lab reports
* lack of pregnancy contraception (women of childbearing potential), pregnancy, or breast feeding.
* Women of childbearing potential not protected by highly effective contraceptive method of birth control OTHER than hormonal contraception (Part 4 only).
* prior significant hearing or kidney problems
* continued toxic effects of prior chemotherapy
* cancers that cannot be physically measured (Part 2 only)

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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)'s of the combination of cabazitaxel and cisplatin (part 1)
timeFrame: first cycle (i.e.3 weeks)
measure: Objective response ratio (Complete response (CR) and partial response (PR)) (part 2)
timeFrame: up to 6 cycles, ie 18 weeks
measure: Pharmacokinetics (PK) of cabazitaxel (part 3 and 4)
timeFrame: up to 6 cycles, ie 18 weeks
Secondary outcomes:
measure: Time to progression (TTP) (part 1 and 2)
timeFrame: up to 6 cycles, ie 18 weeks
measure: Duration of response (DR) (Part 1 and 2)
timeFrame: up to 6 cycles, ie 18 weeks
measure: Cabazitaxel pharmacokinetic (part 1 and 2)
timeFrame: up to 6 cycles, ie 18 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Investigational Site Number 840008
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840003
state: California
city: Decatur
country: United States
facility: Investigational Site Number 840010
state: Illinois
city: Baltimore
country: United States
facility: Investigational Site Number 840002
state: Maryland
city: St Louis
country: United States
facility: Investigational Site Number 840006
state: Missouri
city: Cincinnati
country: United States
facility: Investigational Site Number 840007
state: Ohio
city: San Antonio
country: United States
facility: Investigational Site Number 840005
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Lockhart AC, Sundaram S, Sarantopoulos J, Mita MM, Wang-Gillam A, Moseley JL, Barber SL, Lane AR, Wack C, Kassalow L, Dedieu JF, Mita AC. Phase I dose-escalation study of cabazitaxel administered in combination with cisplatin in patients with advanced solid tumors. Invest New Drugs. 2014 Dec;32(6):1236-45. doi: 10.1007/s10637-014-0145-y. Epub 2014 Aug 13.