Clinical trial NCT01165385: Study With Pazopanib in Combination With Cisplatin (CDDP) in Patients With Advanced Solid Tumors
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Metastatic Cancer
Keywords: Relapsed or refractory solid tumors
Pazopanib
Cisplatin
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2010-07-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities
timeFrame: cycles 1 and 2
Secondary outcomes:
measure: Objective response - Overall Objective response rate - Clinical Benefit Rate
timeFrame: At baseline and every 6 weeks.
measure: To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin
timeFrame: Cycles 1 and 2
Other outcomes:
Locations:
city: Caen
country: France
facility: Centre François BACLESSE
city: Dijon
country: France
facility: Centre Georges François LECLERC
city: Lyon
country: France
facility: Centre Léon Berard
city: Nantes Saint Herblain
country: France
facility: Centre René Gauducheau
city: Paris
country: France
facility: Institut Curie
Study officials:
affiliation: Institut Curie
name: Veronique DIERAS, MD
role: STUDY_CHAIR
References:
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.