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) - Full Text View

Purpose

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	Intervention	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
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cisplatin Carboplatin Gemcitabine Gemcitabine hydrochloride Pemetrexed Pemetrexed disodium Ramucirumab

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Progression-Free Survival (PFS) [ Time Frame: Randomization to PD or death (up to 24 months) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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) ] [ Designated as safety issue: No ]
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 89 weeks of treatment and 1 month post-treatment follow-up ] [ Designated as safety issue: No ]
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.
Squamous Population OS [ Time Frame: Randomization to the date of death from any cause [up to end of study (November 2015)] ] [ Designated as safety issue: No ]
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.

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) ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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).


Enrollment:	280
Study Start Date:	September 2010
Estimated Study Completion Date:	November 2015
Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IMC-1121B + Pemetrexed + Carboplatin (AUC 6) or Cisplatin IMC-1121B + Pemetrexed + Carboplatin [Area Under the Concentration Time Curve 6 (AUC 6)] or Cisplatin	Biological: IMC-1121B (ramucirumab) 10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1 Other Names: ramucirumab IMC-1121B LY3009806 Drug: Pemetrexed 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle Other Name: ALIMTA® 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
Active Comparator: Pemetrexed + Carboplatin (AUC 6) or Cisplatin Pemetrexed + Carboplatin (AUC 6) or Cisplatin	Drug: Pemetrexed 500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle Other Name: ALIMTA® 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
Experimental: IMC-1121B + Gemcitabine + Carboplatin (AUC 5) or Cisplatin IMC-1121B + Gemcitabine + Carboplatin [Area Under the Concentration Time Curve 5 (AUC 5)] or Cisplatin	Biological: IMC-1121B (ramucirumab) 10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1 Other Names: ramucirumab IMC-1121B LY3009806 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
Active Comparator: Gemcitabine + Carboplatin (AUC 5) or Cisplatin Gemcitabine + Carboplatin (AUC 5) or Cisplatin	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

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01160744

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

More Information

No publications provided


Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01160744 History of Changes
Other Study ID Numbers:	13916, I4T-IE-JVBL, CP12-0917, 2009-016784-11
Study First Received:	July 8, 2010
Results First Received:	December 17, 2014
Last Updated:	December 17, 2014
Health Authority:	United States: Food and Drug Administration Canada: Health Canada United Kingdom: Medicines and Healthcare Products Regulatory Agency Belgium: Federal Agency for Medicinal Products and Health Products Poland: Ministry of Health Germany: Paul-Ehrlich-Institut

Keywords provided by Eli Lilly and Company:


Lung neoplasms Lung cancer Non-small Cell Lung Cancer pemetrexed	ALIMTA® squamous nonsquamous

Additional relevant MeSH terms:


Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms Carcinoma, Bronchogenic Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Carboplatin Cisplatin Gemcitabine Pemetrexed	Anti-Infective Agents Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antiviral Agents Enzyme Inhibitors Folic Acid Antagonists Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Radiation-Sensitizing Agents Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015