Chemotherapy and Erlotinib for Lung Cancer With Low Abundance Epidermal Growth Factor Receptor Mutation

Study Overview
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Brief Summary
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This is a single arm phase II clinical trial, which aims to evaluate the effectiveness of intercalated combination of doublet chemotherapy of paclitaxel plus carboplatin and erlotinib on patients with advanced stage non-small-cell lung cancer with low abundant activating EGFR mutation.

Detailed Description
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Primary therapy stage: Paclitaxel Patients receive six cycles of Paclitaxel (175 mg/m² on days 1 of a 4 week cycle, intravenously) plus carboplatin (AUC=5, intravenously on day 1 of a 4 week cycle, intravenously) with sequential erlotinib (150 mg/day) on days 8-21 of each cycle. Maintenance therapy stage: Patients, who complete 6 cycles of therapy without progression or intolerable toxicity, receive erlotinib (150 mg/day) as maintenance therapy until progression, intolerable toxicity or death.

Official Title
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Intercalated Combination of Chemotherapy and Erlotinib in 1st Line Setting for Patients Advanced Stage Non-small-cell Lung Cancer With Low Abundant Activating EGFR Mutation(INNOVATE)

Conditions
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Non-small-cell Lung Cancer

Intervention / Treatment
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* Drug: Intercalated combination of chemotherapy and erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:Patients with histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer. Low abundant activating EGFR mutation: EGFR exon 19 deletion or exon 21 L858R, which are positive by real-time PCR methods and negative by standard sequencing methods. Uncommon EGFR mutations are included excluding exon 20 mutations. ECOG performance status of ≤ 2. Patients can administer first line setting of platinum based chemotherapy. Patients must have measurable disease according to the RECIST (version 1.1) criteria. Life expectancy of at least 12 weeks. Age ≥ 18 years. Written (signed) informed Consent to participate in the study. Adequate organ function as defined by the following criteria: Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN. Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl. Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula). For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Exclusion Criteria:Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments. Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer). Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks. Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids. Nursing or lactating women. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Unwilling to write informed consent to participate in the study. Patients who is unwilling to accept the follow-up.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemotherapy and erlotinib<br>Intercalated combination of chemotherapy and erlotinib in 1st line setting for patients with advanced stage non-small-cell lung cancer with low abundant activating EGFR mutation | Drug: Intercalated combination of chemotherapy and erlotinib<br>* Primary therapy stage: Paclitaxel Patients receive six cycles of Paclitaxel (175 mg/m² on days 1 of a 4 week cycle, intravenously) plus carboplatin (AUC=5, intravenously on day 1 of a 4 week cycle, intravenously) with sequential erlotinib (150 mg/day) on days 8-21 of each cycle. Maintenance therapy stage: Patients, who complete 6 cycles of therapy without progression or intolerable toxicity, receive erlotinib (150 mg/day) as maintenance therapy until progression, intolerable toxicity or death.<br>* Other names: paclitaxel plus carboplatin and targeted therapy erlotinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival defined by imagery methods | From start of anti-cancer therapy untill progression or death | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities related to anti-cancer therapy | From start of anti-cancer therapy till progression of death | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, erlotinib, chemotherapy