Carboplatin, Pemetrexed, and Panitumumab in Patients With Advanced Non-Squamous K-ras Wild Type NSCLC
Condition: Non-Small-Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin; Pemetrexed; Panitumumab
Intervention description: Carboplatin AUC=6IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length); Pemetrexed 500mg/m² IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length); Panitumumab 9mg/kg IV, Day 1 of Cycles 1-6 (Cycles are 3 weeks / 21 days in length)
Intervention MeSH terms: Carboplatin; Pemetrexed; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small-Cell Lung Cancer; NSCLC; Panitumumab; Vectibix; Pemetrexed; Alimta; Carboplatin

Summary:

      The purpose of this multicenter, Phase II trial is to examine the role of a well-tolerated
      novel agent, panitumumab, in combination with a modern platinum doublet regimen using
      carboplatin and pemetrexed, in patients with advanced non-squamous wild type K-ras
      non-small-cell lung cancer (NSCLC). If this treatment proves to be well tolerated and
      associated with efficacy, this would provide rationale for further randomized studies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years.

          2. Histologically confirmed non-squamous NSCLC (squamous cell histology is ineligible).
             Cytologic specimens obtained by brushings, washings or needle aspiration of the
             defined lesion are acceptable. Sputum cytology alone is not acceptable. Mixed tumors
             with small cell elements are not eligible.

          3. Newly diagnosed unresectable stage IIIB or stage IV disease. Patients with stage IIIB
             disease should be ineligible for combined modality therapy (i.e., pleural effusions,
             pericardial effusions, etc.).

          4. At least one unidimensionally measurable lesion definable by magnetic resonance
             imaging (MRI) or computed tomography (CT) scan. Measurable disease is defined by the
             Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

          5. Demonstration of K-ras wild type in archived tumor tissue. Tissue must be available
             for testing or results from previous K-ras testing must be available at the time of
             registration.

          6. No prior antineoplastic chemotherapy for metastatic lung cancer. Patients may have
             received adjuvant treatment for stage I, II or III disease.

          7. For patients who have had previous radiotherapy as definitive therapy for locally
             advanced NSCLC, recurrence must be outside of the original radiation therapy port.
             Radiation therapy must have been completed more than four weeks prior to study entry.
             Previous radiation must have covered < 30% of marrow bearing area.

          8. Full recovery from surgery for patients who have undergone thoracotomy. Patients
             cannot start protocol treatment until at least three weeks after an operative
             procedure.

          9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

         10. Life expectancy ≥ 12 weeks.

         11. Normal bone marrow function within 7 days prior to initial treatment as defined by:

               -  absolute neutrophil count (ANC) ≥1500/µL

               -  platelets ≥100,000/µL

               -  hemoglobin ≥8.0 g/dL. Patients may receive transfusions or erythropoietin to
                  maintain or exceed this level.

         12. Normal hepatic function as defined by:

               -  bilirubin ≤1.5 x institutional upper limit of normal (ULN).

               -  transaminases ≤2.5 x institutional ULN. In the presence of known hepatic
                  metastases, transaminases may be ≤5 x institutional ULN.

         13. Normal renal function within 7 days prior to initial treatment as defined by:

               -  serum creatinine <2.0 mg/dL

               -  estimated creatinine clearance (CrCl) ≥ 45 mL/min calculated by the
                  Cockcroft-Gault method.

         14. Normal metabolic function as follows:

             • Magnesium ≥ institutional lower limit of normal (LLN)

         15. The ability to take folic acid, vitamin B12, and dexamethasone according to the
             protocol.

         16. The ability to interrupt non-steroidal anti-inflammatory drugs (NSAIDs) 2 days before
             (5 days for long-acting NSAIDs), the day of, and 2 days following administration of
             pemetrexed.

         17. Negative serum or urine pregnancy test within 7 days prior to initial study treatment.

         18. Agreement of women of child-bearing potential (WOCBP) and men to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) to prevent
             contraception during treatment and for a minimum of 6 months after the last study
             treatment.

         19. Willingness and ability to comply with study and follow-up procedures.

         20. Ability to understand the nature of this study and give written informed consent.

        Exclusion Criteria:

          1. NSCLC with squamous cell histology.

          2. History of any invasive cancer treated within the previous 5 years with the exception
             of the disease under study, curatively treated non melanoma skin cancer or carcinoma
             in situ of the cervix.

          3. Prior therapy which specifically and directly targets the EGFR pathway (e.g.,
             cetuximab, gefitinib, erlotinib, lapatinib).

          4. Active brain or meningeal metastases. Patients must have completed any previous
             radiotherapy at least four weeks prior to study entry and recovered from any toxicity
             associated with radiotherapy. Patients must have no on-going requirement for and must
             have discontinued corticosteroids.

          5. Pregnancy or breast-feeding.

          6. A serious active infection at the time of treatment or other serious underlying
             medical condition that would impair the ability of the patient to receive protocol
             treatment.

          7. Acute hepatitis or known human immunodeficiency virus (HIV) infection.

          8. Presence of third space fluid which is clinically significant and cannot be controlled
             by drainage.

          9. History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or any
             evidence of interstitial lung disease on baseline chest CT scan).

         10. History of any medical or psychiatric condition or laboratory abnormality that in the
             opinion of the investigator may increase the risks associated with the study
             participation or investigational product(s) administration or may interfere with the
             interpretation of the results.

         11. Prior severe infusion reaction to a monoclonal antibody or history of allergic
             reactions attributed to compounds of similar chemical or biologic composition to
             agents used in study (e.g., carboplatin, pemetrexed).