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

NCT ID: NCT00528281

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-20
• Study Completion Date: 2009-05-27

Brief 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 Patients withdrawn from study treatment with stable disease will be assessed every 6 weeks until progression.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.

Conditions

Lung Cancer, Non-Small Cell

Keywords

Non Small Cell Lung Cancer (NSCLC); Pemetrexed,; Lapatinib (GW572016),

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lapatinib + pemetrexed

This is a single-arm, two-stage, multicenter Phase II study to determine the clinical activity of pemetrexed with lapatinib.

Group Type: EXPERIMENTAL

Lapatinib

Intervention Type: DRUG

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

Intervention Type: DRUG

Pemetrexed is administered intravenously on a 21 day schedule. Two dose levels are used in the dose escalation: 400 and 500 mg.

Interventions

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.

Intervention Type: DRUG

Pemetrexed

Pemetrexed is administered intravenously on a 21 day schedule. Two dose levels are used in the dose escalation: 400 and 500 mg.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, Germany

GSK Investigational Site

Orbassano (TO), Piedmont, Italy

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

Countries

Germany; Italy; Poland; United Kingdom

References

Ramlau R, Thomas M, Novello S, Plummer R, Reck M, Kaneko T, Lau MR, Margetts J, Lunec J, Nutt J, Scagliotti GV. Phase I Study of Lapatinib and Pemetrexed in the Second-Line Treatment of Advanced or Metastatic Non-Small-Cell Lung Cancer With Assessment of Circulating Cell Free Thymidylate Synthase RNA as a Potential Biomarker. Clin Lung Cancer. 2015 Sep;16(5):348-57. doi: 10.1016/j.cllc.2015.01.004. Epub 2015 Jan 20.

Reference Type: BACKGROUND

PMID: 25700774 (View on PubMed)

Other Identifiers

EGF109462

Identifier Type: -

Identifier Source: org_study_id