A Study of Thymidylate Synthase Expression in Patients With Non-Small Cell Lung Cancer

An Exploratory, Prospective Phase II Study to Investigate Progression-Free Survival, Response and Overall Survival Seen With Pemetrexed/Cisplatin and the Role of Thymidylate Synthase Expression

Thymidylate synthase (TS) is a substance the body produces naturally. The purpose of this research is to determine if there is a link between TS production and how well patients respond to treatment of non-squamous non-small cell lung cancer (NSCLC). The aim for the future is that doctors could have a better understanding in advance about which patients might respond well to pemetrexed based on how much TS they produce.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: cisplatin

Detailed Description

All patients on this study will receive 4 intravenous injections of the chemotherapy drugs pemetrexed and cisplatin (with each injection approximately 3 weeks apart). Patients who complete 4 such injections and respond well to their treatment may continue to receive an injection of chemotherapy drug pemetrexed (approximately every 3 weeks). In general terms, treatment will last until either the patient or the doctor decides that there is no clear benefit in continuing with the treatment.

TS levels will be measured from the tumour sample used to make the original diagnosis of NSCLC.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland
    • 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.
• United Kingdom
  • Grimsby, United Kingdom
    • 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.
  • Manchester, United Kingdom, M23 9LT
    • 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.
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • 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.
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • 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.
  • Kent
    • Maidstone, Kent, United Kingdom, ME16 9QQ
      • 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.
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 9HT
      • 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.
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L14 3PE
      • 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.
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • 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.
  • North Lincolnshire
    • Scunthorpe, North Lincolnshire, United Kingdom, DN15 7BH
      • 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.
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 7BL
      • 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.
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PD
      • 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.
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • 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.
  • West Midlands
    • Wolverhampton, West Midlands, United Kingdom, WV10 0QP
      • 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:

• Patients must have Stage 3B or 4 Non-Small Cell Lung Cancer of the non- squamous type
• Patients must at least be able to be physically mobile, take care of yourself and be able to perform light activities such as light housework or office work
• Patients must not have had previous chemotherapy treatment for lung cancer
• Patients must not have had radiotherapy in the last 30 days
• Patients must have measureable tumor lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated on computed tomography (CT) scan
• Patients' test results assessing the function of their blood forming tissue, kidneys, liver and lungs are satisfactory
• Women must be sterile, postmenopausal or on contraception and men must be sterile or on contraception

Exclusion Criteria:

• Patients cannot have received other investigational drugs within the last 30 days
• Patients cannot have any serious, uncontrolled medical condition that might compromise their ability to take part in the study safely
• Patients cannot have a current second primary malignant tumor
• Patients cannot be having current treatment with any other anti-tumor therapy
• Patients cannot have had a yellow fever vaccination within 30 days of enrolment
• Patients who are unable to take vitamins (including injections of vitamin B12) or oral cortisone medication
• Patients who are unable to stop taking more than 1.3 grams of aspirin on a daily basis or non-steroidal anti-inflammatory agents
• Patients who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pemetrexed

Drug: pemetrexed; Induction Therapy: 500 milligrams per square meter (mg/m^2), intravenous, day 1 of each 21 day cycle for the first 4 cycles; Maintenance Therapy: 500 milligrams per square meter (mg/m^2), intravenous, day 1 of each 21 day cycle until progression or unacceptable toxicity occurs; Other Names: Alimta; LY231514; Drug: cisplatin; Induction Therapy: 75 mg/m^2, intravenous, day 1 of each 21 day cycle for the first 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is time from first dose to first observation of disease progression/death (any cause). PFS is reported for participants with thymidylate synthase (TS) scores. For participants not known to have died by the data cut-off date and who do not have progressive disease, PFS will be censored at date of last objective progression-free disease assessment. For participants who receive systemic anticancer therapy after study drug discontinuation and prior to disease progression/death, PFS will be censored at date of last objective progression-free disease assessment prior to chemotherapy.	Baseline to measured progressive disease with follow-up every 6 weeks until progression of disease (up to 18 months after the last participant commenced induction therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Tumor Response (Tumor Response Rate)	Tumor response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. Percentage of participants with tumor response was determined by the number of participants with PR or CR (confirmed or not) divided by the total number of treated participants multiplied by 100.	Baseline to disease progression (up to 20 months)
Percentage of Participants With Concordance Between Local and Central Histological Diagnosis	A centralized pathology review on all enrolled participants was performed to confirm the histological diagnosis performed at the site. Upon review of the local diagnosis obtained at the respective site, the central reviewer established whether or not there was an agreement between the local and central diagnosis. The percentage of participants with concordance was defined as the number of participants for which there was an agreement divided by the number of treated participants (concordance rate) multiplied by 100.	Baseline
Percentage of Participants Surviving at 18 Months (Overall Survival Rate)	The percentage of participants surviving at 18 months was defined as the number of treated participants who had not died prior to 18 months from the date of their first dose divided by the total number of treated participants multiplied by 100. For participants who are alive, overall survival was censored at the last contact.	Baseline to date of death (up to 24.5 months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Fennell DA, Myrand SP, Nguyen TS, Ferry D, Kerr KM, Maxwell P, Moore SD, Visseren-Grul C, Das M, Nicolson MC. Association between gene expression profiles and clinical outcome of pemetrexed-based treatment in patients with advanced non-squamous non-small cell lung cancer: exploratory results from a phase II study. PLoS One. 2014 Sep 24;9(9):e107455. doi: 10.1371/journal.pone.0107455. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: April 23, 2009
• First Submitted That Met QC Criteria: April 23, 2009
• First Posted (Estimate): April 24, 2009

Study Record Updates

• Last Update Posted (Estimate): June 19, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 13069; H3E-BP-JMIK (Other Identifier: Eli Lilly and Company)