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

NCT00984425 | Completed Phase 1

• 1 other identifier: ONC-2008-005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• To determine the dose limiting toxicities (DLTs)and the maximum tolerated dose (MTD) of the combination of Lapatinib and Sorafenib.

  0ne year

Secondary Outcomes (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

  one year

Study Arms (4)

Lapatinib and Sorafenib 1° level of dose

EXPERIMENTAL

Lapatinib 750 mg/die + Sorafenib 200 mg bid

Drug: Lapatinib and Sorafenib

Lapatinib and Sorafenib 2° level of dose

EXPERIMENTAL

2° level (II cohort): Lapatinib 1000 mg/die + Sorafenib 200 mg bid

Drug: Lapatinib and Sorafenib

Lapatinib and Sorafenib 3° level of dose

EXPERIMENTAL

3° level (III cohort): Lapatinib 1000 mg/die + Sorafenib 400 mg bid

Drug: Lapatinib and Sorafenib

Lapatinib and Sorafenib 4° level of dose

EXPERIMENTAL

4° level (IV cohort): Lapatinib 1250 mg/die + Sorafenib 400 mg bid

Drug: Lapatinib and Sorafenib

Interventions

Lapatinib and Sorafenib DRUG

Comparison of different dosages of two drug

Also known as: Tykerb and Nexavar

Lapatinib and Sorafenib 1° level of dose; Lapatinib and Sorafenib 2° level of dose; Lapatinib and Sorafenib 3° level of dose; Lapatinib and Sorafenib 4° level of dose

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinco Humanitas

Rozzano, Milano, 20089, Italy

Location

Related 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 pharmacodynamic study of lapatinib in combination with sorafenib in patients with advanced refractory solid tumors. Eur J Cancer. 2013 Mar;49(5):989-98. doi: 10.1016/j.ejca.2012.10.016. Epub 2012 Nov 9.

  PMID: 23146956 RESULT

MeSH Terms

Interventions

Lapatinib; Sorafenib

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Armando Santoro, MD

  Istituto Clinico Humanitas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2009
• First Posted: September 25, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: August 1, 2013
• Last Updated: December 2, 2014

Record last verified: 2014-11

Locations

IT (1)