Topotecan and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Did Not Respond to Previous Systemic Chemotherapy
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: bevacizumab; topotecan hydrochloride
Intervention description: Will be given by intravenous (IV) infusion at the dose of 10 mg/kg on days 1 and 15 after topotecan administration until disease progression or for another reason.; Topotecan 4 mg/m^2 intravenously (IV) will be given as a 30-minute intravenous infusion on days 1, 8, and 15 with a rest on day 22. Treatment will be repeated every 28 days until disease progression or for another reason.
Intervention MeSH terms: Bevacizumab; Topotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer; large cell lung cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Monoclonal antibodies, such as Avastin (bevacizumab), can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. Giving topotecan together with
      bevacizumab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving topotecan together with bevacizumab
      works in treating patients with stage IIIB or stage IV non-small cell lung cancer that did
      not respond to previous systemic chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed non-small cell lung
             cancer (NSCLC). Patients with extrathoracic-only squamous cell NSCLC are eligible.
             Intrathoracic squamous cell carcinoma will not be eligible. Mixed tumors will be
             categorized by the predominant cell type unless small cell elements are present, in
             which case the patient is ineligible.

          -  Disease that has failed one or more prior standard therapy and is no longer likely to
             respond to such therapy.

          -  Prior systemic chemotherapy, immunotherapy, or biological therapy is allowed, except
             for prior use of Avastin and topotecan in combination. Patient must be at least 14
             days from previous radiation or systemic therapy (at least 30 days for investigational
             agents) and have recovered from the acute toxic effects of the treatment prior to
             study enrollment.

          -  Disease status must be measurable or evaluable as defined by Response Evaluation
             Criteria In Solid Tumors (RECIST criteria)

          -  Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1

          -  Age 18 years or greater

          -  Adequate organ function within 14 days of study registration including the following:

               -  Adequate bone marrow reserve:

                    -  absolute neutrophil count (ANC) > or = to 1.5 x 10^9/L,

                    -  platelets >100 x 10^9/L,

                    -  hemoglobin > 9 g/dL

               -  Hepatic:

                    -  bilirubin <1.5 times the upper limit of normal (x ULN),

                    -  alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine
                       transaminase (ALT) <3.0 x ULN (ALP, AST, and ALT <5 x ULN is acceptable if
                       liver has tumor involvement)

               -  Renal:

                    -  serum creatinine < 2.0

                    -  urine dipstick for proteinuria < 2+ (patients discovered to have ≥2+
                       proteinuria on dipstick urinalysis at baseline should undergo a 24 hour
                       urine collection and must demonstrate ≤ 1g of protein in 24 hours to be
                       eligible)

               -  Coagulation:

                    -  International Normalized Ratio (INR) < 1.5

                    -  Partial thromboplastin time (PTT) < the upper limits of normal (ULN)

          -  Women of childbearing potential and sexually active males are required to use an
             effective method of contraception (ie, a hormonal contraceptive, intra-uterine device,
             diaphragm with spermicide, condom with spermicide, or abstinence) during the study and
             for 3 months after the last dose of study drug.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care.

        Exclusion Criteria:

          -  Pregnant (positive pregnancy test) or breast-feeding. Topotecan is pregnancy category
             D - clear evidence of risk in pregnancy; Avastin is pregnancy category C - risk in
             pregnancy cannot be ruled out. Pregnancy testing is not required for post-menopausal
             or surgically sterilized women

          -  Known hypersensitivity to any component of Avastin (bevacizumab)

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
             diastolic blood pressure > 100 mmHg)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to Day 1

          -  History of stroke or transient ischemic attack within 6 months prior to Day 1

          -  Known central nervous system (CNS) disease, except for treated brain metastasis.
             Treated brain metastases are defined as having no evidence of progression or
             hemorrhage after treatment and no ongoing requirement for dexamethasone, as
             ascertained by clinical examination and brain imaging (MRI or CT) during the screening
             period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may
             include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or
             equivalent) or a combination as deemed appropriate by the treating physician. Patients
             with CNS metastases treated by neurosurgical resection or brain biopsy performed
             within 3 months prior to Day 1 will be excluded

          -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to Day 1

          -  History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month
             prior to Day 1

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Active malignancy other than non-small cell lung cancer (NSCLC), treated superficial
             basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix
             within last five years are allowed.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1 or anticipation of need for major surgical procedure during the course
             of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to Day 1

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 1

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Inability to comply with study and/or follow-up procedures