The Treatment of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors

Solid Tumors Clinical Trial

Official title:

Phase I and Pharmacokinetics Study of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00984425
• Other study ID #: ONC-2008-005
• Status: Completed
• Phase: Phase 1
• First received: September 24, 2009
• Last updated: November 26, 2014
• Start date: September 2009
• Est. completion date: August 2013

Study information

• Verified date: November 2014
• Source: Istituto Clinico Humanitas
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Over the last decade, improvements in the investigators' understanding of the molecular basis of cancer have led to the clinical development of protein kinase inhibitors, which target pivotal molecules involved in intracellular signaling pathways implicated in tumorigenesis and tumor progression. Lapatinib is an oral selective and reversible inhibitor of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor type 2 (HER-2), which are both frequently altered in human malignant tumors. Sorafenib is an oral multi-kinase inhibitor with a dual-action that prevents tumor cell proliferation and angiogenesis. The investigators suggest that through a complete blockade of ErbB signaling network it may be possible to ''sensitize'' tumor cells to antiangiogenic therapy, by lowering the tumor cell survival threshold, while through inhibition of vascular endothelial growth factor (VEGF) pathway to circumvent the problem of acquired resistance to EGFR inhibitors. Based on this theoretical rationale we decide to test the combination of Lapatinib and Sorafenib. This phase I trial will be undertaken to assess the maximum dose tolerated (MTD), safety/tolerability, pharmacokinetics and antitumor efficacy of this combination in patients with advanced, recurrent or metastatic solid cancers refractory to available standard treatment.

Description:

This is a dual-agent, prospective, open-label, multi-centric, phase I trial of combination of Lapatinib and Sorafenib in patients with locally advanced, recurrent or metastatic solid tumors. This trial will be conducted to determine the maximum tolerated dose (MTD), safety/tolerability, pharmacokinetics, and antitumor activity of these two agents given together on a continuous schedule, in patients with advanced solid tumors.

Our ambition is to recommend a safe dose regimen of the combination for subsequent larger phase II studies, coinciding with the maximum tolerated dose (MTD).

The maximum tolerated dose (MTD), will be defined as the highest dosage cohort at which no more than one of six patients will be experienced a DLT in the first treatment cycle.

Eligible patients will be enrolled and treated according to the schema, using a 3+3 design (Fibonacci method modified);

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with locally advanced, recurrent or metastatic histologically confirmed malignancy refractory to available standard treatment

Exclusion Criteria:

• Prior treatment with Lapatinib, Sorafenib or any agents targeting EGFR (other than trastuzumab), Raf, VEGF, or VEGFR

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Lapatinib and Sorafenib
Comparison of different dosages of two drug

Locations

Country	Name	City	State
Italy	Istituto Clinco Humanitas	Rozzano	Milano

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Simonelli M, Zucali PA, Lorenzi E, Rubino L, De Vincenzo F, De Sanctis R, Perrino M, Mancini L, Di Tommaso L, Rimassa L, Masci G, Zuradelli M, Suter MB, Bertossi M, Fattuzzo G, Giordano L, Roncalli MG, Santoro A. Phase I pharmacokinetic and pharmacodynami — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib.		0ne year	No
Secondary	To determine the safety profile of escalating doses of Lapatinib in combination with escalating doses of Sorafenib and and to compare the pharmacokinetics of Lapatinib alone and in combination with Sorafenib		one year	No