This is an open-label, multicenter, non-randomized, phase 1 dose escalation clinical trial to determine the MTD (Maximal Tolerated Dose) of Pazopanib in a population of frail elderly patients, selected according to the International Society of Geriatric Oncology (SIOG)classification (Group 2). It is expected that a total number of 30 patients maximum will be enrolled in the study on 30 months : 18 months accrual - 12 months follow up. Eligible patients will be enrolled into a standard 3+3 design with a starting dose of Pazopanib administered orally at 400 mg per day, in 28-day cycles. Then, further dose levels will be explored. Toxicity of the schedule will be assessed during the first cycle. Patients will receive study medication until disease progression. After treatment discontinuation, patients will be followed during one year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Pazopanib will be administered orally at the starting dose of 400 mg/day in 28-days cycles ; barring limiting toxicities the dose of pazopanib will escalate in several steps (a maximum of 3 dose levels are defined : 400, 600 and 800 mg/day). The pazopanib will be administered at the same dosa until disease progression.
Hôpital Saint André
Bordeaux, France
Centre François BACLESSE
Caen, France
Centre Léon BERARD
Lyon, France
Institut Claudius REGAUD
Toulouse, France
Dose limiting toxicity (DLT) incidence (according DLT definition) during the first treatment cycle with pazopanib (28 days)
The MTD (Maximum Tolerated Dose) is defined as the highest dose level for which 6 patients were treated with a maximum of 1 patient presenting a DLT during the first cycle of treatment
Time frame: 7.5 years
Safety and tolerability assessments using the descriptions and grading scales found in the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0 NCI
Time frame: 7.5 years
Measure of Pazopanib plasma concentration during treatment period (objective : assessment of pharmacokinetics of Pazopanib in this population)
Plasma concentrations of pazopanib will be determined using a validated LC-MS-MS method -
Time frame: .8 time points (cycle 1 Day 1), 3 time points (cycle 1 D15) and 1 pre dose time point each day 1 of the following cycles (over a period of 7.5 years for measures in all patients)
Geriatric criteria measured by comprehensive geriatric assessment which evaluate medical, functional and psychosocial aspects of elderly patients
The impact of treatment on the geriatric assessment will be done using : * G8 : screening test * ADL: Activities Daily Living * IADL: Instrumental Activities Daily Living * MMSE: Mini-mental State Examination * SPPB: Short Physical Performance Battery * MNA: Mini-nutritional Assessment * CAM: Confusion Assessment Method * GDS-15: Geriatric Depression Scale * CIRS-G: Cumulative Illness Rating Scale for Geriatrics,
Time frame: 7.5 years
Rate of objective response according to RECIST criteria
Tumor assessment will be performed at screening visit, every 2 cycles and at the end of study visit and anytime if clinically indicated
Time frame: 7.5 years
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