Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors (PACIFIK)
Primary Purpose
Solid Tumors, Metastatic Cancer
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
cisplatin
Pazopanib
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumors focused on measuring Relapsed or refractory solid tumors, Pazopanib, Cisplatin
Eligibility 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
Sites / Locations
- Centre François BACLESSE
- Centre Georges François LECLERC
- Centre Léon Berard
- Centre René Gauducheau
- Institut Curie
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pazopanib and Cisplatin
Arm Description
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
Outcomes
Primary Outcome Measures
Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities
Secondary Outcome Measures
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01165385
Brief Title
Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Metastatic Cancer
Keywords
Relapsed or refractory solid tumors, Pazopanib, Cisplatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pazopanib and Cisplatin
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
Cisplatinum
Intervention Description
60, 75 or 100 mg/m2 , day 1 - 3 weekly
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
GW76034
Intervention Description
400 mg, 600 mg or 800 mg/day, daily
Primary Outcome Measure Information:
Title
Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities
Time Frame
cycles 1 and 2
Secondary Outcome Measure Information:
Title
Objective response - Overall Objective response rate - Clinical Benefit Rate
Description
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.
Time Frame
At baseline and every 6 weeks.
Title
To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin
Description
The objective of the pharmacokinetics is to investigate the interactions between cisplatin IV and pazopanib
Time Frame
Cycles 1 and 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veronique DIERAS, MD
Organizational Affiliation
Institut Curie
Official's Role
Study Chair
Facility Information:
Facility Name
Centre François BACLESSE
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Georges François LECLERC
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Centre Léon Berard
City
Lyon
ZIP/Postal Code
69373 CEDEX 08
Country
France
Facility Name
Centre René Gauducheau
City
Nantes Saint Herblain
ZIP/Postal Code
44805
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75248
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
28261651
Citation
Dieras V, Bachelot T, Campone M, Isambert N, Joly F, Le Tourneau C, Cassier P, Bompas E, Fumoleau P, Noal S, Orsini C, Jimenez M, Imbs DC, Chatelut E. A Phase I, Dose-Escalation Trial of Pazopanib in Combination with Cisplatin in Patients with Advanced Solid Tumors: A UNICANCER Study. Oncol Ther. 2016;4(2):211-223. doi: 10.1007/s40487-016-0027-x. Epub 2016 Aug 18.
Results Reference
derived
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Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors
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