Multimodality Treatment for Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) - BEACON Study: Bevacizumab and Chemotherapy for Operable NSCLC
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Pre-surgical Treatment with Bevacizumab plus Chemotherapy; Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab
Intervention description: On Cycle 1 Day 1,patient will receive bevacizumab 15 mg/kg. On Cycle 1 Day 15, patients receive docetaxel (75 mg/m2), cisplatin (75 mg/m2). Cycle 2 begins 21 days after administration of docetaxel and cisplatin in Cycle 1. In Cycles 2 thru 3, patients will receive 2 preoperative 21-day cycles of docetaxel (75 mg/m2), cisplatin (75 mg/m2), and bevacizumab (15 mg/kg), all given on Day 1 of each cycle. The sequence of administration will be docetaxel, followed by cisplatin, followed by bevacizumab according to MSKCC Chemotherapy Guidelines. In Cycle 4 Day 1, patients will receive docetaxel (75 mg/m2) and cisplatin (75 mg/m2). Bevacizumab will not be given with Cycle 4. During Cycle 4, the only scheduled clinic visit will be on Day 1. Surgery will occur at least 42 days after the last treatment with bevacizumab. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally 2 weeks after it is scheduled, if necessary.; Patients will receive preoperative 21-day cycles of cisplatin (75 mg/m2) and docetaxel (75 mg/m2) both given on Day 1 of each cycle.Patients will undergo repeat CT imaging after 2 cycles of therapy and patients with at least 10% reduction in bidimensional tumor volume will receive 2 additional neoadjuvant cycles of therapy (total 4 cycles of therapy).Surgery will occur at least 4 weeks after the last treatment with docetaxel and cisplatin.Adjuvant bevacizumab (15 mg/kg q21 days for 1 year, total 18 cycles) will be administered to all patients who undergo resection. Adjuvant bevacizumab will begin between days 42 and 56 after surgery.Patients may be referred for post-operative radiation therapy at the discretion of the treating physician. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally 2 weeks after it is scheduled, if necessary.
Intervention MeSH terms: Bevacizumab; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multi-modality treatment for lung cancer; Carcinoma, Squamous Cell; Bevacizumab; BEACON; 05-052

Summary:

      This is a phase II, single institution trial for patients with clinical Stage IB-IIIA NSCLC
      (T1-3N0-2M0) who have resectable lung tumors. The primary goal of this study is to show that
      the addition of bevacizumab to a cisplatin-based chemotherapy in the neoadjuvant setting for
      non-squamous cell carcinomas improves the rate of pathologic downstaging, which correlates
      with survival. Downstaging is defined as any decrease in the final pathologic stage compared
      with the clinical stage before induction therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologic confirmation of NSCLC at Memorial Sloan-Kettering Cancer Center (MSKCC)

          -  Stages IB, IIA, IIB or IIIA (T1-3N0-2M 0) NSCLC

          -  Patients must be candidates for resection with curative intent.

          -  Measurable disease, defined as at least one lesion that can be accurately measured in
             at least two dimensions

          -  Age >= 18 years

          -  Karnofsky performance status >= 70%

          -  Normal marrow function: leukocytes >= 3,000/µl; absolute neutrophil count ≥ 1,500µl;
             platelets >= 100,000 µl; hemoglobin >= 9gm/dl.

          -  Adequate renal function, with creatinine <= 1.3 mg/dl or calculated creatinine
             clearance >= 60ml/min by Cockcroft-Gault equation using parameters of age, weight
             (kg), and baseline serum creatinine (mg/dl)

          -  Adequate hepatic function: total bilirubin within normal limits; AST <= 1.5 X upper
             limit of normal (UNL); ALT <= 1.5 X UNL; alkaline phosphatase <= 1.5 X UNL.

          -  Women of childbearing age must have a negative urine or blood pregnancy test.

          -  Men and women of childbearing potential must be willing to consent to using effective
             contraception while on treatment and for at least 3 months thereafter.

          -  Patients must have ability to understand and the willingness to sign a written
             informed consent document.

          -  Eligibility criteria for group B: Patients with SQUAMOUS CELL carcinoma or patients
             with a NON-SQUAMOUS CELL tumor with a large central tumor in proximity to significant
             blood vessels or any history of hemoptysis will be assigned to group B (preoperative
             chemotherapy alone without bevacizumab).

        Exclusion Criteria:

          -  Prior chemotherapy or radiation therapy for NSCLC

          -  Prior treatment with bevacizumab or other agents specifically targeting vascular
             endothelial growth factor (VEGF)

          -  Patients with a history of severe hypersensitivity reaction to docetaxel (Taxotere) or
             other drugs formulated with polysorbate 80

          -  Patients with known hypersensitivity to other recombinant human antibodies

          -  Patients must not be receiving any other investigational agents.

          -  History of stroke or transient ischemic attack (TIA).

          -  History of myocardial infarction or unstable angina within the past 12 months.

          -  Patients who report a hearing deficit at baseline, even if it does not require a
             hearing aid or intervention, or interfere with activities of daily life (Common
             Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher)

          -  Peripheral neuropathy > grade 1.

          -  Uncontrolled hypertension

          -  Esophageal varices, non-healing ulcer, wound, or bone fracture

          -  Known HIV-positive patients receiving combination anti-retroviral therapy are excluded
             from the study because of possible pharmacokinetic interactions with the study drugs.

          -  Other serious illness or medical condition including unstable cardiac disease
             requiring treatment, history of significant neurologic or psychiatric disorders
             (including psychotic disorders, dementia, or seizures), symptomatic diverticulitis, or
             active uncontrolled infection.

          -  Women who are pregnant or breast-feeding

          -  Psychiatric illness or social situation that would limit compliance with study
             requirements

          -  Exclusion criteria for group A: Patients with SQUAMOUS CELL carcinoma, large central
             tumor in proximity to significant blood vessels, or any history of hemoptysis (will be
             excluded from group A (preoperative chemotherapy plus bevacizumab); these patients
             will be assigned to group B (preoperative chemotherapy).