A Study of Necitumumab and Chemotherapy in Participants With Stage IV Squamous Non-Small Cell Lung Cancer

Phase 2

Completed

Conditions: Squamous Non Small Cell Lung Cancer

Interventions: Drug: Necitumumab
Drug: Paclitaxel
Drug: Carboplatin

Registration Number: NCT01769391

Lead Sponsor: Eli Lilly and Company

Brief Summary: The main purpose of this study is to evaluate if necitumumab added to standard chemotherapy of paclitaxel and carboplatin is more effective to treat cancer than the standard chemotherapy of paclitaxel and carboplatin alone.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 167

Inclusion Criteria

Histologically or cytologically confirmed squamous NSCLC
Stage IV disease at time of study entry based on American Joint Committee on Cancer (AJCC) 7th edition
Measurable disease at time of study entry as defined by Response Evaluation Criteria in Solid Tumors, (RECIST) Version 1.1
Archived or recent tumor tissue (minimum of 5 unstained tissue slides or a paraffin-embedded tissue block) available for analysis of epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry (IHC) and other biomarker assessments

Exclusion Criteria

Nonsquamous NSCLC
Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
Previous chemotherapy for NSCLC
Major surgery or received any investigational therapy in the 4 weeks prior to randomization
Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Necitumumab +Paclitaxel+Carboplatin	Necitumumab	Necitumumab 800 milligram (mg) administered intravenously (IV) on Days 1 and 8 of every 3 week cycle. Paclitaxel 200 milligram per square meter (mg/m²) administered IV on Day 1 of every 3 week cycle. Carboplatin Area Under the Curve (AUC)6 (mg•min/mL) administered IV on Day 1 of every 3 week cycle. The combination of paclitaxel-carboplatin and necitumumab may continue for a maximum of 6 cycles. Necitumumab may continue until Progressive Disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
Necitumumab +Paclitaxel+Carboplatin	Paclitaxel	Necitumumab 800 milligram (mg) administered intravenously (IV) on Days 1 and 8 of every 3 week cycle. Paclitaxel 200 milligram per square meter (mg/m²) administered IV on Day 1 of every 3 week cycle. Carboplatin Area Under the Curve (AUC)6 (mg•min/mL) administered IV on Day 1 of every 3 week cycle. The combination of paclitaxel-carboplatin and necitumumab may continue for a maximum of 6 cycles. Necitumumab may continue until Progressive Disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
Necitumumab +Paclitaxel+Carboplatin	Carboplatin	Necitumumab 800 milligram (mg) administered intravenously (IV) on Days 1 and 8 of every 3 week cycle. Paclitaxel 200 milligram per square meter (mg/m²) administered IV on Day 1 of every 3 week cycle. Carboplatin Area Under the Curve (AUC)6 (mg•min/mL) administered IV on Day 1 of every 3 week cycle. The combination of paclitaxel-carboplatin and necitumumab may continue for a maximum of 6 cycles. Necitumumab may continue until Progressive Disease (PD), toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.
Paclitaxel + Carboplatin	Paclitaxel	Paclitaxel 200 mg/m² administered IV on Day 1 of every 3 week cycle. Carboplatin AUC=6 administered IV on Day 1 of every 3 week cycle. The combination of paclitaxel-carboplatin may continue for a maximum of 6 cycles. After completion of chemotherapy, participants will be followed until radiographic documentation of PD.
Paclitaxel + Carboplatin	Carboplatin	Paclitaxel 200 mg/m² administered IV on Day 1 of every 3 week cycle. Carboplatin AUC=6 administered IV on Day 1 of every 3 week cycle. The combination of paclitaxel-carboplatin may continue for a maximum of 6 cycles. After completion of chemotherapy, participants will be followed until radiographic documentation of PD.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])	Baseline to Disease Progression or Death (Up to 24 Months)	The denominator of ORR (Objective Response Rate) includes each participant enrolled who received any amount of study drug (necitumumab, gemcitabine, and/or cisplatin), and who had a complete radiographic assessment at baseline and at least one complete radiographic assessment post-baseline. The numerator includes those participants counted in the denominator with a confirmed best overall tumor response of partial or complete response (Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter.) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Randomization to Date of Death (Up to 24 Months)	OS defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date (last contact for participants in post-discontinuation = last known alive date in mortality status).
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab	Pre-infusion Cycle 1, Day 1; Cycle 3, Day 1; Cycle 5; Day 1 (within 2 hours prior to beginning of infusion)
Percentage of Participants With Anti Necitumumab Antibodies	Baseline to End of Cycle 6
Progression-Free Survival	Randomization to Progressive Disease or Death (Up to 24 Months)	Progression-Free Survival (PFS) is defined as the time from randomization until the first radiographically documented progressive disease (PD) or death from any cause. PD defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST version 1.1) as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment.
Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])	Baseline to Progressive Disease and/or Death (Estimated up to 24 Months)	Defined using the same denominator as defined in ORR. Among participants counted in the denominator, the numerator counts those with a confirmed best tumor response of SD, PR, or CR per RECIST 1.1. (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PR at least 30% decrease in the sum of diameter of target lesions; CR: disappearance of all target lesions).
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab	Cycle 1, Day 8 ; Cycle 2, Day 1; Cycle 3, Day 1;Cycle 4, Day1;Cycle 5, Day 1; Cycle 6, Day 1 (within 2 hours prior to beginning of infusion)
Percent Change in Tumor Size (CTS)	Baseline to Progressive Disease or Death (Up to 24 Months)	CTS is defined as maximum percent change from baseline in the sum of target lesions.

Trial Locations

Locations (1): 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.
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Saint Petersburg, Russian Federation