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

NCT00528281 | Completed Phase 1

• 1 other identifier: EGF109462
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 5

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 Patients withdrawn from study treatment with stable disease will be assessed every 6 weeks until progression.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

Outcome Measures

Primary Outcomes (1)

• OTR of the combination of lapatinib and pemetrexed

Secondary Outcomes (2)

• anti-tumour activity of lapatinib in terms of overall response rate

• anti-tumour activity of lapatinib in terms of duration of response, time to response, time to progression, overall survival

Study Arms (1)

Lapatinib + pemetrexed

EXPERIMENTAL

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

Drug: Lapatinib; Drug: Pemetrexed

Interventions

Lapatinib 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.

Lapatinib + pemetrexed

Pemetrexed DRUG

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

Lapatinib + pemetrexed

Eligibility Criteria

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

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Orbassano (TO), Piedmont, 10043, Italy

Location

GSK Investigational Site

Poznan, 60-569, Poland

Location

GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25700774 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Lapatinib; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2007
• First Posted: September 12, 2007
• Study Start: September 20, 2007
• Primary Completion: May 27, 2009
• Study Completion: May 27, 2009
• Last Updated: November 17, 2017

Record last verified: 2017-11

Locations

DE (2); PL (1); IT (1); GB (1)