Phase I Clinical and Pharmacokinetic Study of Pazopanib in a Population of Frail Elderly Patients According SIOG Criteria (VOTRAGE)
Recruitment status was: Recruiting
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.
Metastatic Cancer (Different Solid Tumour Types)
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Clinical and Pharmacokinetic Study of Pazopanib in a Population of Frail Elderly Patients According SIOG Criteria|
- Dose limiting toxicity (DLT) incidence (according DLT definition) during the first treatment cycle with pazopanib (28 days) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]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
- 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: 4 years ] [ Designated as safety issue: Yes ]
- Measure of Pazopanib plasma concentration during treatment period (objective : assessment of pharmacokinetics of Pazopanib in this population) [ 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 4 years for measures in all patients) ] [ Designated as safety issue: No ]Plasma concentrations of pazopanib will be determined using a validated LC-MS-MS method -
- Geriatric criteria measured by comprehensive geriatric assessment which evaluate medical, functional and psychosocial aspects of elderly patients [ Time Frame: 4 years ] [ Designated as safety issue: No ]
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,
- Rate of objective response according to RECIST criteria [ Time Frame: 4 years ] [ Designated as safety issue: No ]Tumor assessment will be performed at screening visit, every 2 cycles and at the end of study visit and anytime if clinically indicated
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||October 2015 (Final data collection date for primary outcome measure)|
Pazopanib : 3 dose levels are defined : 400, 600 and 800 mg per day.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01642017
|Hôpital Saint André|
|Bordeaux, France, 33075|
|Centre François BACLESSE|
|Caen, France, 14076|
|Centre Léon BERARD|
|Lyon, France, 69008|
|Institut Claudius REGAUD|
|Toulouse, France, 31052|
|Principal Investigator:||Loïc MOUREY, PhD||Institut Claudius Regaud|