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)
Overview
- Phase
- Phase 2
- Intervention
- Cetuximab
- Conditions
- Non Small Cell Lung Cancer (NSCLC)
- Sponsor
- University of Pittsburgh
- Enrollment
- 40
- Locations
- 31
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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
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.
Investigators
Ahmad Tarhini
Associate Professor of Medicine and Translational Science
University of Pittsburgh
Eligibility Criteria
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
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.
Arms & Interventions
Cetuximab
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
Intervention: Cetuximab
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to 36 months
Secondary Outcomes
- Progression-free Survival (PFS)(Up to 36 months)
- Best Overall Response Rate (ORR) (Number of Participants)(Up to 12 weeks after treatment initiation)
- EGFR (Epidermal Growth Factor Receptor) Gene Mutation and Akt, pAkt, and MAPKinase(approx. 5 years)