Molecular Profiling in Lung Cancer Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00191308
First received: September 12, 2005
Last updated: October 13, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Carcinoma
Drug: pemetrexed
Drug: cisplatin
Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Profiling and Safety Study of Operable Lung Cancer Patients Treated With Alimta Combined With Cisplatin as Neoadjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • High/Low Expression of Selected Molecular Markers in Tumor Tissues and Hypermethylated Genes in Peripheral Blood [ Time Frame: Baseline, Cycle 2, and surgery (4-8 weeks after last dose of pemetrexed) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Tumor Response (Response Rate) [ Time Frame: Treatment start to disease progression or surgery (4-8 weeks after last dose of pemetrexed) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response [ Time Frame: Time of response to disease progression (up to 44.4 months) ] [ Designated as safety issue: No ]
    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.

  • Disease Free Survival (DFS) [ Time Frame: Treatment start to disease progression or death from any cause (up to 45.5 months) ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) [ Time Frame: Treatment start to death from any cause (up to 47.6 months) ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: May 2005
Study Completion Date: December 2010
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • LY231514
  • Alimta
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00191308

Locations
Poland
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.
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
Sponsors and Collaborators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00191308     History of Changes
Other Study ID Numbers: 9356, H3E-PL-S051
Study First Received: September 12, 2005
Results First Received: March 16, 2010
Last Updated: October 13, 2011
Health Authority: Poland: Ministry of Health

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 17, 2014