Phase II Clinical Study of Weekly Topotecan in Combination With Avastin™ in Patients With Stage IIIB/IV Non-Small Cell Lung Cancer Who Have Failed Prior Systemic Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Lung Cancer
- Sponsor
- Masonic Cancer Center, University of Minnesota
- Enrollment
- 46
- Locations
- 2
- Primary Endpoint
- Median Time to Disease Progression
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief 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.
Detailed Description
OBJECTIVES: Primary * Determine the progression-free survival of patients with stage IIIB or IV non-small cell lung cancer treated with topotecan hydrochloride and bevacizumab who have failed prior systemic chemotherapy. Secondary * Determine the objective response rates in patients treated with this regimen. * Measure time-to-event efficacy variables, including time to objective tumor response (for responding patients), duration of response (for responding patients), time to treatment failure, and overall survival. * Characterize the quantitative and qualitative toxicities of this regimen in these patients. OUTLINE: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days 1, 8, and 15 and Avastin (bevacizumab) IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 6 months from registration.
Investigators
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,
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
Arms & Interventions
Patients Treated With Topotecan and Avastin in NSCLC
Weekly topotecan hydrochloride and bi-weekly Avastin (bevacizumab) in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Intervention: bevacizumab
Patients Treated With Topotecan and Avastin in NSCLC
Weekly topotecan hydrochloride and bi-weekly Avastin (bevacizumab) in patients with non-small cell lung cancer (NSCLC) who have failed prior systemic chemotherapy.
Intervention: topotecan hydrochloride
Outcomes
Primary Outcomes
Median Time to Disease Progression
Time Frame: From Day 1 Until First Documented Disease Progression or Date of Death (Whichever Occurred First)
Assessed by Response Evaluation Criteria In Solid Tumor (RECIST criteria). Progression is defined as a measureable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions since baseline.
Secondary Outcomes
- Median Duration of Response(Day of 1st Response Until Disease Progression of Death/Last Contact)
- Median Overall Survival(From Day 1 Until Death Occurred)
- Number of Tumor Responders(From Day 1 Until Disease Progression or Date of Death (Whichever Occurred First), Up to 1 Year)
- Median Time to Response(From Day 1 Until Tumor Response)