E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced squamous non small cell lung cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to estimate the objective response rates (ORR; complete response [CR] +
partial response [PR]) associated with the study treatments of paclitaxel-carboplatin plus necitumumab (Arm A)
and paclitaxel-carboplatin (Arm B) in chemotherapy-naïve patients with Stage IV squamous cell NSCLC. |
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E.2.2 | Secondary objectives of the trial |
• to assess the relationship between EGFR protein expression (as measured by IHC) and each of several efficacy measures: OS, PFS, best tumor response, disease control rate, and change in tumor size;
• to evaluate OS, PFS, DCR, and CTS between treatment arms;
• to evaluate the safety profile of necitumumab in combination with paclitaxel-carboplatin chemotherapy;
• to characterize pharmacokinetics of necitumumab (Arm A only); and
• to determine the immunogenicity of necitumumab (Arm A only).
Exploratory objectives are to further evaluate the relationships between biomarkers (related to the EGFR-pathway,
NSCLC etiology, and the mechanism of action of necitumumab) and efficacy and safety outcomes, as follows:
• Tumor Tissue: Biomarkers that may include, but not be limited to, HER2 and HER3 protein expression (measured by IHC), and EGFR gene copy number
(measured by FISH);
• Whole Blood: FCγR single-nucleotide polymorphisms (by PCR-based method);
• Plasma Proteomics.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Histologically or cytologically confirmed squamous NSCLC
Stage IV disease at time of study entry based on AJCC 7th edition
Measurable disease at time of study entry as defined by RECIST 1.1
Archived or recent tumor tissue (minimum of 5 unstained tissue slides or a paraffin-embedded tissue
block) available for analysis of EGFR protein expression by IHC and other biomarker assessments. |
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E.4 | Principal 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
(patients who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic
and no longer require treatment with steroids or anticonvulsants, are eligible) |
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E.5 End points |
E.5.1 | Primary end point(s) |
to estimate ORR for each of the 2 study treatment arms |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• to assess the relationship between EGFR protein expression (as measured by immunohistochemistry [IHC]) and each of several efficacy measures: overall survival
(OS), progression-free survival (PFS), best tumor response, disease control rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD]), and
change in tumor size (CTS);
• to evaluate OS, PFS, DCR, and CTS between treatment arms;
• to evaluate the safety profile of necitumumab in combination with paclitaxelcarboplatin chemotherapy;
• to characterize pharmacokinetics of necitumumab (Arm A only); and
• to determine the immunogenicity of necitumumab (Arm A only). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Korea, Republic of |
Mexico |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Defined as the point at which a sufficient number of OS events (deaths) have been observed for final analysis, and the last patient has discontinued study treatment and completed the 30-day safety follow-up visit.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |