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)

Lilly

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Gemcitabine; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin (AUC 6); Drug: Carboplatin (AUC 5); Biological: IMC-1121B (ramucirumab)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01160744

13916

CP12-0917 (Other Identifier)

2009-016784-11 (EudraCT Number)

I4T-IE-JVBL (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 280 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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280 participants in 4 patient groups

IMC-1121B + Pemetrexed + Carboplatin (AUC 6) or Cisplatin

Experimental group

Description:

IMC-1121B + Pemetrexed + Carboplatin \[Area Under the Concentration Time Curve 6 (AUC 6)\] or Cisplatin

Treatment:

Biological: IMC-1121B (ramucirumab)

Drug: Pemetrexed

Drug: Cisplatin

Drug: Carboplatin (AUC 6)

Pemetrexed + Carboplatin (AUC 6) or Cisplatin

Active Comparator group

Description:

Pemetrexed + Carboplatin (AUC 6) or Cisplatin

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Carboplatin (AUC 6)

IMC-1121B + Gemcitabine + Carboplatin (AUC 5) or Cisplatin

Experimental group

Description:

IMC-1121B + Gemcitabine + Carboplatin \[Area Under the Concentration Time Curve 5 (AUC 5)\] or Cisplatin

Treatment:

Biological: IMC-1121B (ramucirumab)

Drug: Cisplatin

Drug: Gemcitabine

Drug: Carboplatin (AUC 5)

Gemcitabine + Carboplatin (AUC 5) or Cisplatin

Active Comparator group

Description:

Gemcitabine + Carboplatin (AUC 5) or Cisplatin

Treatment:

Drug: Cisplatin

Drug: Gemcitabine

Drug: Carboplatin (AUC 5)