A Study of Pemetrexed and Carboplatin/Cisplatin or Gemcitabine and Carboplatin/Cisplatin With or Without IMC-1121B in Participants Previously Untreated With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)
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| ClinicalTrials.gov Identifier: NCT01160744 |
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Recruitment Status :
Completed
First Posted : July 12, 2010
Results First Posted : December 29, 2014
Last Update Posted : September 13, 2019
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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Brief Summary:
The purpose of this study is to determine if participants with Stage IV NSCLC have a better outcome when treated with IMC-1121B in combination with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin than when treated with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin alone.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Carcinoma, Non-Small-Cell Lung | Biological: IMC-1121B (ramucirumab) Drug: Pemetrexed Drug: Carboplatin (AUC 6) Drug: Cisplatin Drug: Gemcitabine Drug: Carboplatin (AUC 5) | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 280 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label, Multicenter, Randomized, Phase 2 Study of a Recombinant Human Anti-VEGFR-2 Monoclonal Antibody, IMC-1121B in Combination With Platinum-based Chemotherapy Versus Platinum-based Chemotherapy Alone as First-line Treatment of Patients With Recurrent or Advanced Non-small Cell Lung Cancer (NSCLC) |
| Study Start Date : | September 2010 |
| Actual Primary Completion Date : | January 2014 |
| Actual Study Completion Date : | April 2018 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: IMC-1121B + Pemetrexed + Carboplatin (AUC 6) or Cisplatin
IMC-1121B + Pemetrexed + Carboplatin [Area Under the Concentration Time Curve 6 (AUC 6)] or Cisplatin
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Biological: IMC-1121B (ramucirumab)
10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1
Other Names:
Drug: Pemetrexed 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle Drug: Carboplatin (AUC 6) Day 1 of every 21-day cycle Drug: Cisplatin 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle |
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Active Comparator: Pemetrexed + Carboplatin (AUC 6) or Cisplatin
Pemetrexed + Carboplatin (AUC 6) or Cisplatin
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Drug: Pemetrexed
500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle Drug: Carboplatin (AUC 6) Day 1 of every 21-day cycle Drug: Cisplatin 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle |
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Experimental: IMC-1121B + Gemcitabine + Carboplatin (AUC 5) or Cisplatin
IMC-1121B + Gemcitabine + Carboplatin [Area Under the Concentration Time Curve 5 (AUC 5)] or Cisplatin
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Biological: IMC-1121B (ramucirumab)
10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1
Other Names:
Drug: Cisplatin 75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle Drug: Gemcitabine 1000 mg/m² on Days 1 and 8 of every 21-day cycle Drug: Carboplatin (AUC 5) Day 1 of every 21-day cycle |
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Active Comparator: Gemcitabine + Carboplatin (AUC 5) or Cisplatin
Gemcitabine + Carboplatin (AUC 5) or Cisplatin
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Drug: Cisplatin
75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle Drug: Gemcitabine 1000 mg/m² on Days 1 and 8 of every 21-day cycle Drug: Carboplatin (AUC 5) Day 1 of every 21-day cycle |
Primary Outcome Measures :
- Progression-Free Survival (PFS) [ Time Frame: Randomization to PD or death (up to 24 months) ]PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization.
Secondary Outcome Measures :
- Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months) ]Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100.
- Overall Survival (OS) [ Time Frame: Randomization to the date of death from any cause (up to 31.3 months) ]OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.
- Duration of Response (DOR) [ Time Frame: Time of first response (CR or PR) until PD or death (up to 24 months) ]DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.
- Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died [ Time Frame: Day 1, Cycle 1 (3-week cycles) Up to 3 Years ]Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Other Outcome Measures:
- Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] [ Time Frame: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months) ]DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100.
- Change in Tumor Size (CTS) [ Time Frame: Baseline, 6 weeks ]CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Confirmed NSCLC
- Stage IV disease at the time of study entry
- Measurable disease at the time of study entry
- Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia)
- Adequate hematologic function, hepatic function, renal function and coagulation function
- If sexually active, must be post-menopausal, surgically sterile, or using effective contraception; and agrees to use adequate contraception during the study period and for up to 6 months after the last dose of study medication
- Female participants of childbearing potential must have a negative serum pregnancy test
Exclusion Criteria:
- Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
- Tumor wholly or partially contains small cell lung cancer
- Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization
- Concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years
- Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR)
- Receiving concurrent treatment with other anticancer therapy
- Has received previous chemotherapy for Stage IV NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
- Has radiologically documented evidence of major blood vessel invasion or encasement by cancer
- Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions)
- Ongoing or active infection
- History of significant neurological or psychiatric disorders
- Experienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmia
- Poorly-controlled hypertension
- Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
- Receiving chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
- Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization
- Major surgery within 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to randomization
- Elective or a planned major surgery
- Pregnant or lactating
- Any other serious uncontrolled medical disorders or psychological conditions
- Allergy / history of hypersensitivity reaction to any of the treatment components
- History of drug abuse
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01160744
Locations
Show 53 study locations
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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT01160744 |
| Other Study ID Numbers: |
13916 I4T-IE-JVBL ( Other Identifier: Eli Lilly and Company ) CP12-0917 ( Other Identifier: ImClone Systems ) 2009-016784-11 ( EudraCT Number ) |
| First Posted: | July 12, 2010 Key Record Dates |
| Results First Posted: | December 29, 2014 |
| Last Update Posted: | September 13, 2019 |
| Last Verified: | August 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting. |
| Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
| URL: | https://vivli.org/ |
Keywords provided by Eli Lilly and Company:
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Lung neoplasms Lung cancer Non-small Cell Lung Cancer |
pemetrexed squamous nonsquamous |
Additional relevant MeSH terms:
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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 Gemcitabine Cisplatin Carboplatin Pemetrexed |
Ramucirumab Antibodies, Monoclonal Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |