First-Line Chemotherapy and Panitumumab in Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the addition of panitumumab to standard chemotherapy in first-line treatment of advanced Non Small Cell Lung Cancer improves the treatment outcome. Patients are selected based on triple mutational status.

Detailed Description
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Advanced NSCLC holds a very poor prognosis with a moderate response rate to standard chemotherapy. The standard first-line treatment for advanced NSCLC is platinum based combination chemotherapy. The response rates are less than 30% and a substantial amount of patients will experience unnecessary toxicity in terms of e.g. nausea, vomiting, neuropathies or a considerable risk of renal toxicity. The median progression free survival is 3-4 months and consequently, the median overall survival is less than one year (Hotta et al 2007). Addition of new biological agents to standard chemotherapy regimens may improve the outcome for these patients.

Official Title
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A Phase II Study of First-Line Chemotherapy and Panitumumab in Advanced NSCLC Selected by Mutational Status

Conditions
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Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Vinorelbine
* Drug: panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic (stage IV) NSCLC Measurable disease according to RECIST v.1.0 2009 KRAS, BRAF and PI3K wild type in primary tumor or metastatic tissue. Age ≥18 PS < 2 Adequate organ function Haematology: Neutrophil count ≥1.5x10^9/L Platelet count ≥100x10^9/L Leucocyte count > 3,000/mm Hepatic function: Total bilirubin ≤ 1.5 times the upper normal limit (UNL) Serum transaminases ≤ 2.5xUNL in absence of liver metastases, or ≤ 5xUNL in presence of liver metastases Renal Function: Creatinine clearance ≥ 50 mL/min and serum creatinine ≤ 1.5xUNL Metabolic function: Magnesium ≥ lower limit of normal. Calcium ≥ lower limit of normal. Consent to translational research studies Written informed consent Exclusion Criteria: Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment/randomization, active severe infections or other concurrent disease. Known CNS metastasis (pretreatment routine assessment not required) Prior chemotherapy for metastatic disease Indication for radiation therapy or prior radiotherapy within 30 days before treatment start. Other malignant diseases within 5 years prior to inclusion in the study, except basal cell squamous carcinoma of the skin and cervical carcinoma-in-situ. Other experimental therapy within 30 days prior to treatment initiation. History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. Patients pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment. Patients (male or female) not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment.

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: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Carboplatin|i.v. day 1: AUC 5 x (GFR + 25) mg q3w|
|Drug: Vinorelbine|i.v. day 1: 30 mg/m2 q3w Orally day 8: 60 mg/m2 q3w|
|Drug: panitumumab|i.v. day 1: 9 mg/kg q3w|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | Up to 3 years | 
| Overall survival |  | Up to 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Non small cell lung cancer, Triple mutational status, KRAS, BRAF, PI3K