Preoperative Chemotherapy and Bevacizumab in Patients With Stage IB (>4 cm), II, or Select Stage III NSCLC
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin; Paclitaxel; Bevacizumab
Intervention description: Carboplatin: AUC=6, given IV on Days 1, 22, 43, and 64; Paclitaxel: 200 mg/m2, given IV on Days 1, 22, 43, and 64; Bevacizumab: 15 mg/kg, given IV on Days 1, 22, and 43 (Note: bevacizumab will not be dosed on Day 64 prior to surgery)
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; NSCLC; Preoperative chemotherapy; Bevacizumab; Avastin

Summary:

      The rationale for this multicenter, phase II trial is to examine the impact of
      carboplatin/paclitaxel with bevacizumab in the preoperative treatment of patients with stage
      IB (> 4.0 cm), II, and select stage III NSCLC. If this novel regimen proves to be safe and
      active in this setting, this would provide rationale for further investigation in a larger,
      prospective, randomized setting.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >=18 years.

          2. Histologically-confirmed NSCLC (adenocarcinoma, large cell, and undifferentiated).
             Patients with squamous histology are not eligible.

          3. Life expectancy of at least 12 weeks.

          4. Patients with the following stages of NSCLC:

               -  T2 N0 tumors: Limited to tumors >=4 cm.

               -  T1-2 N1 tumors.

               -  T3 N0-1 tumors (excluding superior sulcus tumors): Including tumors involving the
                  chest wall, proximal airway, or mediastinal pleura where preoperative RT is not
                  planned.

               -  T1-2 N2 tumors: For patients with N2 disease involving 1 zone (Upper zone (R), AP
                  zone (L), subcarinal zone, or lower zone) and nodes <=2 cm in diameter.

               -  T4 N0-1 tumors (excluding superior sulcus tumors): T4 lesions, other than
                  malignant effusions where radiotherapy is not planned.

          5. Patients with clinical N2 involvement must have histologic confirmation by
             mediastinoscopy (or alternate biopsy procedure).

          6. Tumors should be considered potentially resectable.

          7. No evidence of extrathoracic metastatic disease.

          8. Patients must have measurable disease by RECIST version 1.1 criteria.

          9. Patients must be candidates (medically) for chemotherapy followed by surgical
             resection.

         10. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time
             of a minor surgery (with the exception of portacath or other central access catheter
             placement); at least 4 weeks must have elapsed from the time of a major surgery.

         11. Laboratory values as follows:

               -  Absolute neutrophil count (ANC) >=1500/µL

               -  Hemoglobin (Hgb) >=9 g/dL

               -  Platelets >=100,000/uL

               -  AST/SGOT and ALT/SGPT within normal limits (WNL)

               -  Total bilirubin within normal limits (WNL)

               -  Creatinine <=1.5 mg/dL

         12. ECOG Performance Status grade 0 or 1.

         13. Women of childbearing potential must have a negative serum or urine pregnancy test
             performed within 7 days prior to start of treatment. Women of childbearing potential
             or men with partners of childbearing potential must use effective birth control
             measures during treatment. If a woman becomes pregnant or suspects she is pregnant
             while participating in this study, she must agree to inform her treating physician
             immediately.

         14. Patient must be accessible for treatment and follow-up.

         15. Patients must be able to understand the investigational nature of this study and give
             written informed consent prior to study entry.

        Exclusion Criteria:

          1. Mixed small-cell and non-small cell histologies.

          2. Pulmonary carcinoid tumors.

          3. History of prior malignancy within 3 years, with the exception of non-melanoma skin
             cancer or carcinoma in situ.

          4. Peripheral neuropathy >= grade 1.

          5. Patients receiving thrombolytic therapy within 10 days of starting study treatment are
             ineligible. Therapeutic anticoagulation is allowed if the anticoagulant dosing is
             stable.

          6. History of acute myocardial infarction or unstable angina within 6 months prior to Day
             1 of study treatment.

          7. History of or stroke or ischemic attack within 6 months prior to Day 1 of study
             treatment.

          8. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
             and/or diastolic blood pressure >100 mmHg) in spite of medical management.

          9. New York Heart Association (NYHA) class II or greater congestive heart failure (CHF).

         10. Patients with significant vascular disease (e.g., aortic aneurysm requiring surgical
             repair, or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of
             study treatment.

         11. Any prior history of hypertensive crisis or hypertensive encephalopathy.

         12. Patients with hematemesis or hemoptysis (>=1/2 teaspoon of bright red blood per
             episode) within 1 month prior to Day 1 of study treatment.

         13. Proteinuria at screening, as demonstrated by either:

               -  Urine protein: creatinine (UPC) ratio >=1.0 (see Appendix A) at screening, or

               -  Urine dipstick for proteinuria >=2+ (patients discovered to have >=2+ proteinuria
                  on dipstick analysis should undergo a 24-hour urine collection and must have <=1g
                  of protein in 24 hours to be eligible).

         14. Patients with a serious non-healing wound, active ulcer, or untreated bone fracture.

         15. Patients with evidence of bleeding diathesis or coagulopathy (in the absence of
             therapeutic anticoagulation).

         16. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 1 of study treatment.

         17. Women who are pregnant (positive pregnancy test) or lactating.

         18. Use of any non-approved or investigational agent within 28 days of administration of
             the first dose of study drug.

         19. Patients may not receive any other investigational or anti-cancer treatments while
             participating in this study.

         20. Concurrent severe, intercurrent illness including, but not limited to, ongoing or
             active infection, or psychiatric illness/social situations that would limit compliance
             with study requirements.

         21. History of hypersensitivity to active or inactive excipients of any component of
             treatment.

         22. Inability to comply with study and/or follow-up procedures.