Molecular Profiling in Lung Cancer Patients

• ClinicalTrials.gov Identifier: NCT00191308
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Results First Posted: April 20, 2010
• Last Update Posted: October 21, 2011
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 19, 2005
• Results First Submitted Date: March 16, 2010
• Results First Posted Date: April 20, 2010
• Last Update Posted Date: October 21, 2011
• Study Start Date: May 2005
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2011)

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) ]

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.

Original Primary Outcome Measures (submitted: September 12, 2005)

• expression of selected molecular markers in the tumor tissue
• presence of selected hypermethylated genes in peripheral blood

Current Secondary Outcome Measures (submitted: October 13, 2011)

• 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) ]
  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) ]
  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) ]
  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) ]
  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.

Original Secondary Outcome Measures (submitted: September 12, 2005)

• to assess tumor response, duration of response, disease free survival(DFS) and overall survival (OS)
• prognostic role of selected molecular markers in tumor tissue on DFS and OS
• how does the neoadjuvant treatment influence the presence of selected hypermethylated genes in peripheral blood
• characterization of the quantitative and qualitative toxicities on pemetrexed and cisplatin in the neoadjuvant setting

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Molecular Profiling in Lung Cancer Patients
• Official Title: Molecular Profiling and Safety Study of Operable Lung Cancer Patients Treated With Alimta Combined With Cisplatin as Neoadjuvant Chemotherapy
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• Carcinoma

Intervention

• 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.

Study Arms

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

Interventions:

• Drug: pemetrexed
• Drug: cisplatin
• Procedure: Radical Non-Small Cell Lung Cancer (NSCLC) surgery

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 16, 2010): 30
• Original Enrollment (submitted: September 12, 2005): 60
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT00191308
• Other Study ID Numbers: 9356; H3E-PL-S051 ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: October 2011