A Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin With Radiation Therapy Followed by Pemetrexed in Patients With Inoperable Non-Small-Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00482014
• Recruitment Status: Completed
• First Posted: June 4, 2007
• Results First Posted: November 27, 2012
• Last Update Posted: November 27, 2012
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The primary purpose of this study is to determine the 2-year survival rate of both of the chemotherapy regimens in patients with inoperable non-small-cell lung cancer.

Condition or disease	Intervention/treatment	Phase
Non-Small-Cell Lung Cancer	Drug: pemetrexed; Drug: cisplatin; Drug: carboplatin; Radiation: radiation therapy	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of Pemetrexed (Alimta) Plus Carboplatin, or Pemetrexed Plus Cisplatin With Concurrent Radiation Therapy Followed by Every-21-Day Pemetrexed Consolidation in Patients With Favorable-Prognosis Inoperable Stage IIIA/B Non-Small-Cell Lung Cancer (NSCLC)
• Study Start Date: May 2007
• Actual Primary Completion Date: October 2011
• Actual Study Completion Date: October 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: A: Pemetrexed + Carboplatin; Pemetrexed + Carboplatin	Drug: pemetrexed; Phase 1 - 500 milligram/meter squared (mg/m²), administered intravenously, every 21 days for 3 cycles Phase 2 - 500 mg/m², administered intravenously, every 21 days for 3 cycles Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation therapy for each phase; Other Names: LY231514; Alimta; Drug: carboplatin; Phase 1 - dosed at area under the curve (AUC) 2 milligram/milliliter*minute (mg/mL*min), administered intravenously, Days 1, 8, 22, 29 and 43 Phase 2 - dosed at AUC 5 mg/mL*min, administered intravenously, every 21 days for 3 cycles; Radiation: radiation therapy; Phase 1 - 2 Gray, daily, 5 days a week for Days 1-51 Phase 2 - 2 Gray, daily, 5 days a week for Days 1-45
Experimental: B: Pemetrexed + Cisplatin; Pemetrexed + Cisplatin	Drug: pemetrexed; Phase 1 - 500 milligram/meter squared (mg/m²), administered intravenously, every 21 days for 3 cycles Phase 2 - 500 mg/m², administered intravenously, every 21 days for 3 cycles Consolidation Therapy - 500 mg/m² pemetrexed, administered intravenously, every 21 days for 3 cycles beginning 3 weeks after completion of chemoradiation therapy for each phase; Other Names: LY231514; Alimta; Drug: cisplatin; Phase 1 - 30 mg/m² and 75 mg/m², administered intravenously, Days 1, 8, 22, 29 and 43 Phase 2 - 75 mg/m², administered intravenously, every 21 days for 3 cycles; Radiation: radiation therapy; Phase 1 - 2 Gray, daily, 5 days a week for Days 1-51 Phase 2 - 2 Gray, daily, 5 days a week for Days 1-45

Outcome Measures

Primary Outcome Measures :

1. Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin [ Time Frame: Phase 1 enrollment to the end of study treatment up to Week 11 ]
   MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis).
2. Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin [ Time Frame: Phase 1 enrollment to the end of study treatment up to Week 11 ]
   MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis).
3. Phase 2 - Survival Probability at 2 Years [ Time Frame: Phase 2 randomization up to 2 years ]

Secondary Outcome Measures :

1. Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Phase 1 enrollment up to Week 11 ]
   Phase 1 pharmacology toxicity was defined as the number of participants experiencing dose limiting toxicities (DLTs). DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) >7 days, febrile neutropenia, ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations), and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). Grade 5 events are the events leading to the death.
2. Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate) [ Time Frame: Phase 1 enrollment to the end of the study treatment up to Week 11 ]
   Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
3. Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events [ Time Frame: Phase 2 randomization to the end of the study treatment up to 30.0 months ]
   Phase 2 pharmacology toxicity was defined as the number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Events section.
4. Phase 2 - Time to Progression [ Time Frame: Phase 2 randomization to measured disease progression up to 24 months ]
   Time to disease progression was measured from randomization of Study Phase 2 to the first observation of disease progression according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Disease progression is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.
5. Phase 2 - Median Survival [ Time Frame: Phase 2 randomization to death as the result of any cause up to 30.0 month ]
6. Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate) [ Time Frame: Phase 2 randomization to the end of the treatment up to 30.0 months ]
   Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Inoperable non small cell lung cancer
• No weight loss greater than 10% in 3 months prior to enrolling in trial
• Adequate kidney function
• Adequate liver function
• Adequate lung function

Exclusion Criteria:

• Previous surgery to remove lung tumor
• Previous chemotherapy or radiation therapy or lung cancer
• Inability to take vitamin supplementation
• Heart attack within past 6 months
• Active infection

Contacts and Locations

Locations

United States, California

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.

Los Angeles, California, United States, 90095

United States, Kansas

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.

Wichita, Kansas, United States, 67214

United States, Missouri

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.

St Louis, Missouri, United States, 63110

United States, Nevada

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.

Las Vegas, Nevada, United States, 89135

United States, North Carolina

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.

Burlington, North Carolina, United States, 27216

United States, Tennessee

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.

Memphis, Tennessee, United States, 38120

United States, Texas

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.

Corpus Christi, Texas, United States, 78405

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.

Dallas, Texas, United States, 75390

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.

Temple, Texas, United States, 76508

India

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.

Delhi, India, 110085

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.

Trivandrum, India, 695 011

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:

Lilly Clinical Trial Registry 

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00482014
• Other Study ID Numbers: 9031; H3E-US-S047 ( Other Identifier: Eli Lilly and Company )
• First Posted: June 4, 2007
• Results First Posted: November 27, 2012
• Last Update Posted: November 27, 2012
• Last Verified: October 2012

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors