Molecular Profiling in Lung Cancer Patients

Molecular Profiling and Safety Study of Operable Lung Cancer Patients Treated With Alimta Combined With Cisplatin as Neoadjuvant Chemotherapy

The main purpose of this study of pemetrexed combined with cisplatin used as neoadjuvant chemotherapy (2 or 3 cycles) in participants with operable non-small cell lung cancer (NSCLC) is to look at various genes present in participants' blood and tumor tissue to see if there is any link between the levels or changes in the genes and how participants with lung cancer respond to pemetrexed and cisplatin treatment.

Study Overview

• Status: Completed
• Conditions: Carcinoma; Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: cisplatin; Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Bystra Slaska, Poland, 43-360
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Poznan, Poland, 60-569
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Warsaw, Poland, 02-781
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• pathologic documentation of non-small cell lung cancer (NSCLC)
• tumor must be accessible by bronchoscopy for tumor tissue sample collection
• patients must have lung cancer with clinical stage IB, II, IIIA
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• patients must not have received prior systemic chemotherapy or radiation therapy for NSCLC (prior resection of lung is allowed provided at least 5 years have elapsed between prior surgery and enrolment)

Exclusion Criteria:

• bronchoalveolar carcinoma or stage IIIA tumor involving the superior sulcus (Pancoast tumors)
• pregnant or breast feeding patients
• patients who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
• patients with history or presence of other malignancy except in situ carcinoma of the skin or prior malignancy treated more than 5 years before without recurrence (excluding melanoma, breast cancer and hypernephroma)
• unwillingness to take folic acid or vitamin B12 supplementation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pemetrexed + Cisplatin; Pemetrexed: 500 milligrams per square meter (mg/m^2) intravenous (IV) every 21 days (q 21 days) for 3 cycles unless disease progression occurs Cisplatin: 75 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs	Drug: pemetrexed; 500 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs; Other Names: Alimta; LY231514; Drug: cisplatin; 75 mg/m^2 IV q 21 days for 3 cycles unless disease progression occurs; Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery; All participants proceeded to surgery within 4-8 weeks from the last dose of pemetrexed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood	Molecular markers assessed by immunohistochemistry: thymidylate synthase, glycinamide ribonucleotide formyl transferase (GARFT), epidermal growth factor receptor (EGFR); and by polymerase chain reaction: dihydrofolate reductase (DHFR), dihydropyrimidine dehydrogenase (DPD), folylpolyglutamate synthetase (FPGS), reduced folate carrier, alpha folate receptor, Excision Repair Cross-Complementation Group 1 (ERCC1), folylpolyglutamate hydrolase (FPGH). Hypermethylated genes assessed by methylation-specific polymerase chain reaction. Due to small sample size, tumor-tissue analyses were not done.	Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Tumor Response (Response Rate)	Tumor response to treatment using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Response rate was estimated as the total number of CR or PR, divided by the total number of participants treated.	Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed)
Duration of Response	The duration of response was defined as the time from complete response (CR) or partial response (PR) to disease progression. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions.	Time of response to disease progression (up to 44.4 months)
Disease Free Survival (DFS)	DFS was the time from date of first dose to first observation of progressive disease (PD) or death due to any cause. PD=20% increase in sum of longest diameter of target lesions. If a participant was not known to have died or have PD, DFS was censored at the date of the last objective progression-free disease assessment.	Treatment start to disease progression or death from any cause (up to 45.5 months)
Overall Survival (OS)	OS was defined as the time from treatment start to death from any cause. For participants who were alive, OS was censored at the last contact date.	Treatment start to death from any cause (up to 47.6 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/ GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• Lilly Clinical Trial Registry

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 19, 2005

Study Record Updates

• Last Update Posted (Estimate): October 21, 2011
• Last Update Submitted That Met QC Criteria: October 13, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 9356; H3E-PL-S051 (Other Identifier: Eli Lilly and Company)