A Phase II Trial of Lapatinib (TYKERB) + Pemetrexed (ALIMTA) in Advanced Non Small Cell Lung Cancer With an Initial Dose Finding Phase

Lung Cancer, Non-Small Cell Clinical Trial

Official title:

A Single-arm, Two-stage Phase II Study of Lapatinib and Pemetrexed in the Second Line Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528281
• Other study ID #: EGF109462
• Status: Completed
• Phase: Phase 1
• First received: September 11, 2007
• Last updated: November 13, 2017
• Start date: September 20, 2007
• Est. completion date: May 27, 2009

Study information

• Verified date: November 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II study is a single-arm, two-stage, multicentre study to determine the clinical activity of lapatinib in combination with pemetrexed in patients with Non-Small Cell Lung Cancer (NSCLC) who have received one prior cytotoxic chemotherapy regimen. There will be a short safety run in portion of the study to determine the optimal treatment regimen (OTR) for the combination, since these two drugs have not previously been used together.

Approximately 27 patients will be enrolled into the first stage of the study and if sufficient responses are seen an additional 27 patients will be enrolled into the second stage giving an overall evaluable patient number of 54. Patients will be treated with pemetrexed plus lapatinib at the determined OTR to disease progression, death or withdrawal from the study treatment for any reason.

Safety and efficacy assessments will be performed on all patients at 6-week intervals, as well as at the end of treatment. Patients withdrawn from study treatment with stable disease will be assessed every 6 weeks until progression. Thereafter, patients will be followed for survival at approximately 12-week intervals until death or to a maximum of 5 years after last patient is enrolled, whichever comes first.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 27, 2009
• Est. primary completion date: May 27, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA:

• Signed informed consent;

• Patients must be 18 years old;

• Subjects must have stage IIIB or IV NSCLC .

• Recurrent or persistent NSCLC following one previous line of cytotoxic chemotherapy.

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2;

• Life expectancy of 12 weeks;

• Have adequate organ function baseline laboratory values for inclusion;

EXCLUSION CRITERIA:

• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;

• Known history of or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or antiseizure medication for = 3 months prior to study enrollment.

• Peripheral neuropathy of grade 3 or higher;

• Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, and tumor embolization).

• Prior exposure to pemetrexed or an EGFR inhibitor in combination with 5-FU or a 5FU prodrug.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-Small Cell
• Lung Neoplasms

Intervention

Drug:
• Lapatinib
Lapatinib was administered once daily orally. Patients will begin treatment at Dose Level 0, using a lower dose of pemetrexed, 400mg (approved dose is 500mg). Absent a DLT or need for treatment delay in cycle 1, Dose level 0 or 1, patients may be dose escalated to dose level 1 or 2, respectively in cycle 2.
• Pemetrexed
Pemetrexed is administered intravenously on a 21 day schedule. Two dose levels are used in the dose escalation: 400 and 500 mg.

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Italy	GSK Investigational Site	Orbassano (TO)	Piemonte
Poland	GSK Investigational Site	Poznan
United Kingdom	GSK Investigational Site	Newcastle upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Italy,  Poland,  United Kingdom, 

References & Publications (1)

Ramlau, R., Thomas, M., Plummer, R., Reck, M., Heussel, C. P., Lau, M., Parikh, R., Kaneko, T., Oliva, C., Novello, S. Phase I study of lapatinib, a dual-tyrosine kinase inhibitor, and pemetrexed in the second-line treatment of advanced or metastatic non-small-cell lung cancer, J Clin Oncol 27, 2009 (suppl; abstr e19027)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	OTR of the combination of lapatinib and pemetrexed
Secondary	anti-tumour activity of lapatinib in terms of overall response rate
Secondary	anti-tumour activity of lapatinib in terms of duration of response, time to response, time to progression, overall survival

External Links

•   Results for study EGF109462 can be found on the GSK Clinical Study Register.