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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by UNICANCER
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01165385
First received: June 25, 2010
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Metastatic Cancer
Drug: cisplatin
Drug: Pazopanib
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 38
Study Start Date: June 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pazopanib and Cisplatin
  • Steady state period:Pazopanib will be given 8 days prior to cisplatin
  • Then pazopanib will be given 400 mg, 600 mg or 800 mg/day, daily and cisplatin 60, 75 or 100 mg/m2 , day 1 - 3 weekly, depending of the dose level
Drug: cisplatin
60, 75 or 100 mg/m2 , day 1 - 3 weekly
Other Name: Cisplatinum
Drug: Pazopanib
400 mg, 600 mg or 800 mg/day, daily
Other Name: GW76034

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165385

Locations
France
Centre François BACLESSE Recruiting
Caen, France, 14076
Contact: Florence Joly    +3.2.31.45.50.02    f.joly@baclesse.fr   
Principal Investigator: Florence Joly         
Centre Georges François LECLERC Recruiting
Dijon, France, 21079
Contact: Nicolas ISAMBERT    +33.3.80.73.77.53    nisambert@cgfl.fr   
Principal Investigator: Nicolas ISAMBERT         
Centre Léon Berard Recruiting
Lyon, France, 69373 CEDEX 08
Contact: Thomas Bachelot, MD    00 33 4 78 78 27 73    bachelot@lyon.fnclcc.fr   
Centre René Gauducheau Recruiting
Nantes Saint Herblain, France, 44805
Contact: Mario Campone, MD    00 33 2 40 67 99 00    m-campone@nantes.fnclcc.fr   
Institut Curie Recruiting
Paris, France, 75248
Contact: Véronique Dieras, MD    33 1 44 32 46 75    veronique.dieras@curie.net   
Contact: Christophe Le Tourneau, MD    00 33 1 44 32 40 86    christophe.letourneau@curie.net   
Sponsors and Collaborators
UNICANCER
Investigators
Study Chair: Veronique DIERAS, MD Institut Curie
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01165385     History of Changes
Other Study ID Numbers: GEP 07/0908 - PACIFIK
Study First Received: June 25, 2010
Last Updated: January 13, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by UNICANCER:
Relapsed or refractory solid tumors
Pazopanib
Cisplatin

Additional relevant MeSH terms:
Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 19, 2014