Multicenter Dose-escalation Study of a Combination of Pazopanib and Bevacizumab in Patients With Metastatic Renal Cell Carcinoma or Others Advanced Solid Tumors (PARASOL)
This is an open-label, multicenter dose-escalation phase I study using a 3+3+3 design (i.e., 3 to 9 patients per dose level) in patients with mRCC or others advanced refractory solid tumors. Enrolment will be performed to include approximately ½ of patients with mRCC.
The primary endpoint is the occurrence of limiting toxicities leading to definitive discontinuation of the study drugs during the first 24 weeks in absence of progression of the disease.
Secondary endpoints included the occurrence of Dose Limiting Toxicities (DLTs) evaluated during the first two cycles; overall response rate, 6-months progression-free survival rate and Pharmacokinetic assessments.
|Metastatic Renal Cell Carcinoma Advanced Refractory Solid Tumors Histologically or Cytologically Confirmed||Drug: Association of Bevacizumab (BVC)+ Pazopanib (PZP)||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Bevacizumab in Patients With Metastatic Renal Cell Carcinoma or Others Advanced Solid Tumors|
- Determination of the Optimal Long Exposure Dose (OLED) [ Time Frame: 24 weeks for each patient ]The primary endpoint is the occurrence of an interruption of one drug of the association of a duration superior to 4 weeks during the first 24 weeks in absence of progression of the disease.
- The determination of the maximum-tolerated dose (MTD) [ Time Frame: 8 weeks for each patient ]
- To estimate the overall response rate (ORR) [ Time Frame: 24 weeks ]
- To estimate the 6-month progression-free survival (PFS) rate [ Time Frame: 24 weeks ]
- To characterize the pharmacokinetic (PK) profile of Pazopanib when combined with Bevacizumab. [ Time Frame: 8 weeks ]
|Study Start Date:||July 2010|
|Study Completion Date:||March 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Drug: Association of Bevacizumab (BVC)+ Pazopanib (PZP)
Treatment is administered in 28-day cycles, during which patients received BVC intravenously every 2 weeks and oral PZP once daily from days 1 to 28. For the first cycle, PZP is administered alone from days 1 to 14.
The starting dose for dose escalation is BVC at 7.5 mg/kg in combination with PZP 400 mg (level 1).
The therapy regimens for each dose level are respectively:
BVC 7.5 mg/kg + PZP 600 mg (level 2) BVC 10 mg/kg + PZP 600 mg (level 3) BVC 10 mg/kg + PZP 800 mg (level 4). Patients who experience grades 3 to 4 adverse events have dose adjustments to one or both drugs. Dose reductions affect in priority the administration of PZP. Doses reductions to PZP are made in 200-mg decrements and to BVC to 2.5-mg/kg decrements.
Patients with toxicities that warrant reductions at either PZP 400 mg or BVC 7.5 mg/kg are withdrawn from the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01202032
|Centre Léon BERARD|
|Lyon, France, 69373|
|Principal Investigator:||SYLVIE NEGRIER, Phd||Centre Léon Bérard; Lyon; FRANCE|