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

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ClinicalTrials.gov Identifier: NCT00984425
Recruitment Status : Completed
First Posted : September 25, 2009
Last Update Posted : December 2, 2014
Sponsor:
Information provided by (Responsible Party):
Istituto Clinico Humanitas

Brief 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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Lapatinib and Sorafenib Phase 1

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);


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : September 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib. [ Time Frame: 0ne year ]

Secondary Outcome Measures :
  1. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications of Results:
Responsible Party: Istituto Clinico Humanitas
ClinicalTrials.gov Identifier: NCT00984425     History of Changes
Other Study ID Numbers: ONC-2008-005
First Posted: September 25, 2009    Key Record Dates
Last Update Posted: December 2, 2014
Last Verified: November 2014

Additional relevant MeSH terms:
Sorafenib
Lapatinib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs