Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors (PACIFIK)
The aim of this research is to evaluate the potential interest of an association of Pazopanib, a multi-tyrosine kinase inhibitor, and cisplatin.
As cisplatin has marketing approval for several cancers (ovarian, testicle, bladder, esophagus, endometrium, lung, stomach, head and neck cancer (HNC)), and in order to have a rapid evaluation of this combination, we will evaluate the combination in any patient whose tumors is known to be sensible to cisplatin (except tumors at risk of bleeding).
This study is a classical phase 1 trial of pazopanib and 3-weekly cisplatin association. It will allow for optimal dose selection and pharmacokinetic analysis. It is planed to include around 38 patients, enriching the optimal tolerated regimen (OTR) level only with a cohort of triple negative breast cancer patients. If the association is proven to be feasible, we will then move to a specific phase II study in triple negative breast cancer patients.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Dose Escalation and Pharmacokinetic Phase I Study With Pazopanib in Combination With Cisplatin (CDDP) Every Three Weeks in Patients With Advanced Solid Tumors|
- Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities [ Time Frame: cycles 1 and 2 ] [ Designated as safety issue: No ]
- Objective response - Overall Objective response rate - Clinical Benefit Rate [ Time Frame: At baseline and every 6 weeks. ] [ Designated as safety issue: No ]Anti-tumor activity of the pazopanib/cisplatin combination will be carried out by the determination of the objective response rate according to RECIST criteria version 1.1.
- To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin [ Time Frame: Cycles 1 and 2 ] [ Designated as safety issue: No ]The objective of the pharmacokinetics is to investigate the interactions between cisplatin IV and pazopanib
|Study Start Date:||June 2010|
|Study Completion Date:||October 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Pazopanib and Cisplatin
60, 75 or 100 mg/m2 , day 1 - 3 weekly
Other Name: CisplatinumDrug: Pazopanib
400 mg, 600 mg or 800 mg/day, daily
Other Name: GW76034
The main objective of the study is to determine the dose limiting toxicities (DLT) and the optimal tolerated regimen (OTR) which are both safety criteria evaluated upon the NCI CTC-AE system version 4.0.
Efficacy is not the primary objective; however the anti-tumor activity of the pazopanib/cisplatin combination will be carried out by the determination of the objective response rate according to RECIST criteria version 1.1.
The objective response is defined as either a complete response (CR) or partial response (PR), assessed either by CT Scan and/or MRI and/or bone Scan, performed at baseline and every 6 weeks.
This is an open-label, non-randomized, dose escalation and pharmacokinetic, phase I study pazopanib with cisplatin in patients with relapsed or refractory solid tumors (except tumors at risk of bleeding) for whom the selected combined chemotherapy is indicated or is a reasonable option (as per tumor characteristics and previous treatments).
All eligible patients entering the study will receive daily oral pazopanib, supplied as 200 mg aqueous film-coated tablets and intravenous cisplatin every three weeks. Doses of both compounds will be adjusted according to the reached dose level.
The treatment will continue until the development of unacceptable toxicity or evidence of disease progression or until patient's / investigator's decision of withdrawal.
All patients who received at least on dose of the study drug will be followed for survival outcome.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01165385
|Centre François BACLESSE|
|Caen, France, 14076|
|Centre Georges François LECLERC|
|Dijon, France, 21079|
|Centre Léon Berard|
|Lyon, France, 69373 CEDEX 08|
|Centre René Gauducheau|
|Nantes Saint Herblain, France, 44805|
|Paris, France, 75248|
|Study Chair:||Veronique DIERAS, MD||Institut Curie|