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

Sponsor
Istituto Clinico Humanitas
Study ID
NCT00984425
Phase
PHASE1
Status
Completed

Conditions

  • Solid Tumors

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Lapatinib and Sorafenib — DRUG
    Comparison of different dosages of two drug

Study Details

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.

Key Dates

Start date
Sep 30, 2009
Status verified
Nov 2014
Primary completion
Jul 31, 2012
Completion
Aug 31, 2013

Study Design

Enrollment
30 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Lapatinib and Sorafenib 1° level of dose
    Lapatinib 750 mg/die + Sorafenib 200 mg bid
  • Experimental: Lapatinib and Sorafenib 2° level of dose
    2° level (II cohort): Lapatinib 1000 mg/die + Sorafenib 200 mg bid
  • Experimental: Lapatinib and Sorafenib 3° level of dose
    3° level (III cohort): Lapatinib 1000 mg/die + Sorafenib 400 mg bid
  • Experimental: Lapatinib and Sorafenib 4° level of dose
    4° level (IV cohort): Lapatinib 1250 mg/die + Sorafenib 400 mg bid

Primary Outcome Measure

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

Related Studies