Study of Cetuximab With Radiation Followed by Consolidation Chemotherapy for NSCLC

Study Overview
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Brief Summary
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This is an open label, phase II study in which cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab will be administered to subjects with locally advanced NSCLC.

Detailed Description
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This is a Phase II study to determine the overall survival for patients with locally advanced NSCLC treated with cetuximab with concurrent thoracic radiotherapy followed by consolidation chemotherapy with paclitaxel/carboplatin/cetuximab. This is a multicenter study including 36 subjects who will be males and females, both greater than 18 years of age. All subjects will initially receive radiation and cetuximab. Radiation will be given once a day (Monday-Friday) for approximately 6-8 weeks. During the course of radiation, cetuximab will be given intravenously once a week. Approximately 4-6 weeks after the last radiation dose, the subjects will be treated with chemotherapy, paclitaxel/carboplatin. Chemotherapy will be given intravenously once every 3 weeks for 3 cycles (1 cycle=3 weeks). Cetuximab intravenous administration will be continued throughout the entire study, once a week through week 26 including during chemotherapy.

Official Title
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A Phase II Study of Cetuximab in Combination With External Beam Radiation Followed By Consolidation Chemotherapy for Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non Small Cell Lung Cancer (NSCLC)

Intervention / Treatment
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* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed diagnosis of non-small cell lung cancer Patients must have surgically unresectable stage IIIA disease or stage IIIB disease without malignant pleural/pericardial effusion Patients must have measurable disease as per the RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See section 9.2 for the evaluation of measurable disease. Age >18 years. Lung cancer is extremely rare in children. ECOG performance status 0-1 (Karnofsky >70%; see Appendix A). If available, tumor tissue should be submitted for EGFR status by IHC and correlative studies. Patients must have normal organ and marrow function as defined below: leukocytes >3,000/μL absolute neutrophil count >1,500/μL platelets >100,000/μL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal The effects of cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because EGFR inhibitors, chemotherapeutic agents and radiation therapy, as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Patients must either be not of child bearing potential or have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Willingness to sign an approved informed consent. Exclusion Criteria: Patients should not have received prior chest radiation therapy. Patients with a history of pulmonary fibrosis are excluded from study. Patients may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, cetuximab or other agents used in the study. History of any cancer other than NSCLC (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last five years. Prior therapy with known specific inhibitors of the EGFR. History of severe allergic reaction to prior therapy with monoclonal antibodies Peripheral neuropathy of more than grade 1 in severity Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, significant history of uncontrolled cardiac disease ie. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure,and cardiomyopathy with decreased ejection fraction, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because carboplatin, paclitaxel, cetuximab and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the above agents, breastfeeding should be discontinued if the mother is treated with the agents used in this study. These potential risks may also apply to other agents used in this study. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with carboplatin, paclitaxel and cetuximab or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Active hepatitis. History of pulmonary fibrosis.

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: Cetuximab<br>Cetuximab 400 mg/m2 IV week 0 only External beam radiation weeks 1 - 7 Cetuximab 250 mg/m2 IV weekly thereafter weeks 1 - 7 Cetuximab 250 mg/m2 IV weekly weeks 8 - 26 Carboplatin AUC = 6 IV Paclitaxel 200 mg/m2 IV Every 3 weeks x 3 Cycles | Drug: Cetuximab<br>* The initial dose of cetuximab is 400 mg/m2 intravenously administered over 120 minutes, followed by weekly infusions at 250 mg/m2 IV over 60 minutes. Subjects will receive cetuximab from week 0 through week 26.<br>* Other names: Erbitux, C225;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Progressive Disease was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Up to 36 months | 
| Best Overall Response Rate (ORR) (Number of Participants) | The Best Overall Response is the best response (Complete Response, Partial Response, Stable Disease, Progressive Disease) recorded from the start of the study treatment until the disease progression/recurrence at end of study. Response and progression were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000]. Complete Response (CR) is the Disappearance of all target lesions and Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | Up to 12 weeks after treatment initiation | 
| EGFR (Epidermal Growth Factor Receptor) Gene Mutation and Akt, pAkt, and MAPKinase | EGFR (epidermal growth factor receptor) gene mutation status and Akt, pAkt, and MAPKinase in participant tumor tissue. | approx. 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non Small Cell Lung Cancer, NSCLC, EGFR Inhibitor, Radiation Therapy