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

NCT01165385 | Completed Phase 1 DMC

• 1 other identifier: GEP 07/0908 - PACIFIK
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Solid Tumors; Metastatic Cancer

Keywords

Relapsed or refractory solid tumors; Pazopanib; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Determination of the Optimal Tolerated Regimen (OTR) based on the occurrence of Dose Limiting Toxicities

  cycles 1 and 2

Secondary Outcomes (2)

• Objective response - Overall Objective response rate - Clinical Benefit Rate

  At baseline and every 6 weeks.

• To characterize the pharmacokinetic (PK) profile of the combination pazopanib and cisplatin

  Cycles 1 and 2

Study Arms (1)

Pazopanib and Cisplatin

EXPERIMENTAL

* 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; Drug: Pazopanib

Interventions

cisplatin DRUG

60, 75 or 100 mg/m2 , day 1 - 3 weekly

Also known as: Cisplatinum

Pazopanib and Cisplatin

Pazopanib DRUG

400 mg, 600 mg or 800 mg/day, daily

Also known as: GW76034

Pazopanib and Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (5)

Centre François BACLESSE

Caen, 14076, France

Location

Centre Georges François LECLERC

Dijon, 21079, France

Location

Centre Léon Berard

Lyon, 69373 CEDEX 08, France

Location

Centre René Gauducheau

Nantes Saint Herblain, 44805, France

Location

Institut Curie

Paris, 75248, France

Location

Related Publications (1)

• 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.

  PMID: 28261651 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence

Interventions

Cisplatin; pazopanib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Veronique DIERAS, MD

  Institut Curie

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2010
• First Posted: July 19, 2010
• Study Start: June 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2014
• Last Updated: November 17, 2014

Record last verified: 2014-11

Locations

FR (5)