Study of Cetuximab With Radiation Followed by Consolidation Chemotherapy for NSCLC
Condition: Non Small Cell Lung Cancer (NSCLC)
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cetuximab
Intervention description: 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.
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non Small Cell Lung Cancer; NSCLC; EGFR Inhibitor; Radiation Therapy

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.
    

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

          -  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.