A Study Comparing of Two Different Chemotherapy Regimens, in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

A Randomized Phase 2 Study Comparing Pemetrexed Plus Best Supportive Care With Best Supportive Care as Maintenance, Following First-Line Treatment With Pemetrexed-Cisplatin, in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

This is a multicenter, open-label, randomized, two-arm Phase 2 study comparing pemetrexed plus best supportive care with best supportive care alone as maintenance therapy following first-line treatment with a pemetrexed-cisplatin combination in patients with advanced non-squamous non-small cell lung cancer.

A total of approximately 100 patients are planned to be enrolled, and following completion of four cycles of pemetrexed-cisplatin (Induction Phase) those patients in which disease progression has not occurred will be randomized in a 2:1 ratio to one of two treatment arms (Maintenance Phase): Arm A (pemetrexed plus best supportive care) or Arm B (best supportive care alone).

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: pemetrexed; Drug: Best Supportive Care

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 0000
    • 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.
  • Cairo, Egypt, 11372
    • 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.
  • Mounofia, Egypt, 32514
    • 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.
• Lebanon
  • Beirut, Lebanon
    • 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.
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • 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:

1. You must be at least 18 years old
2. You must have been diagnosed with non-squamous non-small cell lung cancer (NSCLC)
3. You must have had no prior systemic anticancer therapy for lung cancer
4. You must live close enough to the study doctor to be able to visit regularly for follow up
5. You must have signed informed consent form indicating your willingness to take part in this study
6. Your laboratory and medical history and tests must meet study requirements

Exclusion criteria:

1. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
2. Prior radiotherapy and surgery should be completed at least 4 weeks prior to initiation of treatment
3. Serious concomitant systemic disorder (e.g., active infection including human immunodeficiency virus, or unstable cardiovascular disease)
4. Prior malignancy other than NSCLC, carcinoma in situ of the cervix, or nonmelanoma skin cancer unless treated at least 5 years previously with no subsequent evidence of recurrence
5. Brain metastasis
6. Presence of clinically significant (by physical exam) third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry
7. Significant weight loss (greater than 10%), over the previous 6 weeks before study entry
8. Concurrent administration of any other antitumor therapy
9. Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents such as piroxicam)
10. Inability or unwillingness to take folic acid, dexamethasone (or equivalent) or vitamin B12 supplementation
11. Pregnancy or breast-feeding
12. You are allergic to pemetrexed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: Pemetrexed + Best Supportive Care; Pemetrexed: 500 milligrams per square meter (mg/m²) , intravenous (IV), Day 1 of each 21-day cycle for 6 cycles Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.	Drug: pemetrexed; 500 mg/m², IV, Day 1 of each 21-day cycle for 6 cycles; Other Names: Alimta; LY231514; Drug: Best Supportive Care; Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.
Active Comparator: B: Best Supportive Care; Best Supportive Care: Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.	Drug: Best Supportive Care; Patients will receive best supportive care (dose, frequency, duration) as judged by their treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival During Maintenance Phase	Progression free survival is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in maintenance phase uses the last lesion assessment prior to randomization as the baseline assessment.	Randomization to progression of disease (PD) or date of death from any cause up to 30.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival During Overall Period (Induction Phase [IP] + Maintenance Phase [MP])	Progression-free survival in overall period is defined as the time from the date of first dose of study drug during IP until the date of PD or death from any cause. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions. PD in overall period uses the screening lesion assessment prior to the induction phase as the baseline assessment.	First dose of study drug during IP to PD or date of death from any cause up to 33.6 months
Overall Survival During Maintenance Phase	Overall survival in maintenance phase is defined as the time from randomization to death. Participants who were alive were censored at the last contact.	Randomization to PD or date of death from any cause up to 31.3 months
Overall Survival During Overall Period (IP + MP)	Overall survival in overall period is defined as the time from first dose of study drug during IP to death. Participants who were alive were censored at the last contact.	First dose of study drug during IP to PD or date of death from any cause up to 34.1 months
Number of Participants With Adverse Events (AEs) During Overall Period	The list of serious adverse events (SAEs) and other non-serious adverse events (AEs) are in Adverse Events Section.	First dose of study drug during IP through overall study completion (up to 34.3) months
Tumor Response Rate and Disease Control Rate After Induction Phase (IP)	Tumor response rate (%) is the number of responders (participants with best response of CR or PR) divided by the number of participants qualified for tumor response according to RECIST criteria multiplied by 100. Disease control rate is percentage of participants with a best response of stable disease [SD], PR, or CR. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; PD is≥20% increase in sum of longest diameter of target lesions. SD= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Randomization to measured PD up to 31.4 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 9am to 5pm Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Mubarak N, Gaafar R, Shehata S, Hashem T, Abigeres D, Azim HA, El-Husseiny G, Al-Husaini H, Liu Z. A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer. BMC Cancer. 2012 Sep 24;12:423. doi: 10.1186/1471-2407-12-423.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: January 17, 2008
• First Submitted That Met QC Criteria: January 31, 2008
• First Posted (Estimate): February 1, 2008

Study Record Updates

• Last Update Posted (Estimate): December 26, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 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; 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: 11839 (DAIDS ES); H3E-EZ-S114 (Other Identifier: Eli Lilly and Company)