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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Istituto Clinico Humanitas.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Istituto Clinico Humanitas
ClinicalTrials.gov Identifier:
NCT00984425
First received: September 24, 2009
Last updated: September 1, 2010
Last verified: September 2010
  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 ]

Estimated Enrollment: 12
Study Start Date: September 2009
Estimated Study Completion Date: September 2010
Primary Completion Date: March 2010 (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
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
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
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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Armando Santoro, MD +39028224 ext 4080 armando.santoro@humanitas.it
Contact: Matteo Simonelli, MD +39028224 ext 4080 matteo.simonelli@humanitas.it

Locations
Italy
Istituto Clinco Humanitas Recruiting
Rozzano, Milano, Italy, 20089
Contact: Armando SAntoro, MD    +30028224 ext 4080    armando.santoro@humanitas.it   
Contact: Matteo Simonelli, MD    +30028224 ext 4080    matteo.simonelli@humanitas.it   
Sub-Investigator: Matteo Simonelli, MD         
Principal Investigator: Armando SAntoro, MD         
Sponsors and Collaborators
Istituto Clinico Humanitas
Investigators
Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas
  More Information

No publications provided by Istituto Clinico Humanitas

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Armando Santoro, MD, 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: September 1, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by Istituto Clinico Humanitas:
Locally advanced, recurrent or metastatic histologically confirmed malignancy refractory to available standard treatment

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

ClinicalTrials.gov processed this record on September 16, 2014