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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Istituto Clinico Humanitas
ClinicalTrials.gov Identifier:
NCT00984425
First received: September 24, 2009
Last updated: November 26, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Solid Tumors
Drug: Lapatinib and Sorafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I and Pharmacokinetics Study of Lapatinib in Combination With Sorafenib in Patients With Advanced Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by Istituto Clinico Humanitas:

Primary Outcome Measures:
  • To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib. [ Time Frame: 0ne year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: September 2009
Study Completion Date: August 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lapatinib and Sorafenib 1° level of dose
Lapatinib 750 mg/die + Sorafenib 200 mg bid
Drug: Lapatinib and Sorafenib
Comparison of different dosages of two drug
Other Name: Tykerb and Nexavar
Experimental: Lapatinib and Sorafenib 2° level of dose
2° level (II cohort): Lapatinib 1000 mg/die + Sorafenib 200 mg bid
Drug: Lapatinib and Sorafenib
Comparison of different dosages of two drug
Other Name: Tykerb and Nexavar
Experimental: Lapatinib and Sorafenib 3° level of dose
3° level (III cohort): Lapatinib 1000 mg/die + Sorafenib 400 mg bid
Drug: Lapatinib and Sorafenib
Comparison of different dosages of two drug
Other Name: Tykerb and Nexavar
Experimental: Lapatinib and Sorafenib 4° level of dose
4° level (IV cohort): Lapatinib 1250 mg/die + Sorafenib 400 mg bid
Drug: Lapatinib and Sorafenib
Comparison of different dosages of two drug
Other Name: Tykerb and Nexavar

Detailed 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);

  Eligibility

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

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00984425

Locations
Italy
Istituto Clinco Humanitas
Rozzano, Milano, Italy, 20089
Sponsors and Collaborators
Istituto Clinico Humanitas
Investigators
Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas
  More Information

Publications:
Responsible Party: Istituto Clinico Humanitas
ClinicalTrials.gov Identifier: NCT00984425     History of Changes
Other Study ID Numbers: ONC-2008-005
Study First Received: September 24, 2009
Last Updated: November 26, 2014
Health Authority: Italy: Ministry of Health

Additional relevant MeSH terms:
Lapatinib
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on June 30, 2015