Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors

Solid Tumors Clinical Trial

— PACIFIK  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01165385
• Other study ID #: GEP 07/0908 - PACIFIK
• Status: Completed
• Phase: Phase 1
• First received: June 25, 2010
• Last updated: November 14, 2014
• Start date: June 2010
• Est. completion date: October 2014

Study information

• Verified date: November 2014
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Main Inclusion Criteria:

• Documented metastatic solid malignancies for patients who are candidate to receive a cisplatin based regimen.

• During the dose seeking procedure : ALL solid tumors

• During the Optimal Tolerated Regimen validation procedure : ONLY HER2-RH- breast cancer

• Measurable or evaluable disease

• WHO performance status = 1

• Negative dipstick proteinuria test or if positive proteinuria <1g/24h. If proteinuria appears = 2+ on routine dipstick testing, patients must undergo a 24H -urine collection and demonstrate proteinuria < 1g/24H

• Corrected QT interval (QTc) = 480 msecs using Bazett's formula

Main Exclusion Criteria:

• Prior treatment with cisplatin reaching a cumulative dose> 300 mg/m2

• HER2 positive breast cancer

• Patients at high risk of bleeding

• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product

• calcium and magnesium levels inferior to standard levels (measured within 14 days before the first pazopanib dose) and potassium levels inferior to standard levels (measured within 72 hours before the first pazopanib dose)

• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study

• Hearing impairment/tinnitus > or = grade 2

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Solid Tumors

Intervention

Drug:
• cisplatin
60, 75 or 100 mg/m2 , day 1 - 3 weekly
• Pazopanib
400 mg, 600 mg or 800 mg/day, daily

Locations

Country	Name	City	State
France	Centre François BACLESSE	Caen
France	Centre Georges François LECLERC	Dijon
France	Centre Léon Berard	Lyon
France	Centre René Gauducheau	Nantes Saint Herblain
France	Institut Curie	Paris

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities		cycles 1 and 2	No
Secondary	Objective response - Overall Objective response rate - Clinical Benefit Rate	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.	At baseline and every 6 weeks.	No
Secondary	To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin	The objective of the pharmacokinetics is to investigate the interactions between cisplatin IV and pazopanib	Cycles 1 and 2	No