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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Multicenter, Open-Label, Phase 2 Study of Paclitaxel-Carboplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Paclitaxel-Carboplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Squamous Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Necitumumab
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Necitumumab +Paclitaxel+Carboplatin<br>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. | Drug: Necitumumab<br>* Administered IV<br>* Other names: IMC-11F8;Drug: Paclitaxel<br>* Administered IV<br>Drug: Carboplatin<br>* Administered IV<br>|
| Active Comparator: Paclitaxel + Carboplatin<br>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. | Drug: Paclitaxel<br>* Administered IV<br>Drug: Carboplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) | 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. | Baseline to Disease Progression or Death (Up to 24 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | 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). | Randomization to Date of Death (Up to 24 Months) | 
| 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 | 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. | Randomization to Progressive Disease or Death (Up to 24 Months) | 
| Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) | 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). | Baseline to Progressive Disease and/or Death (Estimated up to 24 Months) | 
| Percent Change in Tumor Size (CTS) | CTS is defined as maximum percent change from baseline in the sum of target lesions. | Baseline to Progressive Disease or Death (Up to 24 Months) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC