A Phase II Study of Prophylactic Radiation Therapy for the Prevention of Hemoptysis in Advanced Non Small Cell Lung Cancer in Combination With Bevacizumab, Paclitaxel, and Carboplatin in Patients at High Risk for Bevacizumab-Associated Hemoptysis
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Adenosquamous Cell Lung Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Safety of treatment as measured by the incidence of grade 3-5 hemoptysis, as assessed by NCI CTCAE version 3.0
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This phase II trial is studying the side effects and how well giving radiation therapy together with bevacizumab, paclitaxel, and carboplatin works in treating patients with unresectable stage IIIB or stage IV non-small cell lung cancer at high risk for hemoptysis caused by bevacizumab. Radiation therapy uses high-energy x-rays to kill tumor cells. It may also prevent hemoptysis caused by bevacizumab. Monoclonal antibodies, such as 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 non-small cell lung cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with bevacizumab and chemotherapy may kill more tumor cells
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate the safety of prophylactic chest radiotherapy, bevacizumab, paclitaxel, and carboplatin in patients with unresectable stage IIIB or IV non-small cell lung cancer at high risk for bevacizumab-associated hemoptysis. SECONDARY OBJECTIVES: I. Assess progression-free survival of patients treated with this regimen. II. Assess the rate of objective response, overall survival, time to response, and response duration in irradiated lesions and non-irradiated lesions in these patients. OUTLINE: This is an open-label, pilot, multicenter study. Patients are assigned sequentially to 1 of 2 treatment strata. Stratum I: Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2). Stratum II: Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 12 months. PROJECTED ACCRUAL: A total of 72 patients will be accrued for this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed primary non-small cell lung cancer (NSCLC)\* meeting the following criteria:
- •Squamous cell or mixed squamous-nonsquamous histology with predominant squamous component (≥ 50% squamous) with a primary, unresected endobronchial lesion
- •No small cell component
- •Centrally located primary tumor, defined by the following:
- •Primary tumor of any T stage within or touching the zone of the proximal bronchial tree
- •Zone is defined as a 3-dimensional volume with a perimeter of 2 cm in each direction around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi)
- •Any disease within this volume must not invade blood vessels determined by a contrast-enhanced CT scan evaluation of the entire thorax with thin slices (≤ 5 mm) through the area of central tumor bulk (i.e., no evidence of vessel invasion radiological evaluation)
- •Stage IIIB (with malignant pleural effusion) or stage IV disease
- •Patients with stage IIIB NSCLC without an effusion are eligible if they are not candidates for combined modality therapy with curative intent (i.e., radical chemoradiotherapy)
- •At high risk for bevacizumab-associated hemoptysis
Exclusion Criteria
- Not provided
Arms & Interventions
Stratum I (radiotherapy, bevacizumab, chemotherapy)
Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2).
Intervention: bevacizumab
Stratum I (radiotherapy, bevacizumab, chemotherapy)
Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2).
Intervention: paclitaxel
Stratum I (radiotherapy, bevacizumab, chemotherapy)
Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2).
Intervention: carboplatin
Stratum I (radiotherapy, bevacizumab, chemotherapy)
Patients undergo prophylactic radiotherapy on days 1-5 and 8-12. Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 15. Patients also receive paclitaxel IV over 3 hours or carboplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 36 (course 2).
Intervention: radiation therapy
Stratum II (radiotherapy, chemotherapy, bevacizumab)
Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
Stratum II (radiotherapy, chemotherapy, bevacizumab)
Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: paclitaxel
Stratum II (radiotherapy, chemotherapy, bevacizumab)
Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
Stratum II (radiotherapy, chemotherapy, bevacizumab)
Patients undergo prophylactic radiotherapy and receive paclitaxel and carboplatin as in stratum I. Patients also receive bevacizumab IV over 30-90 minutes on day 15 (course 1). In both strata, treatment with paclitaxel, carboplatin, and bevacizumab repeats every 21 days for 5-6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may continue to receive single-agent bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention: radiation therapy
Outcomes
Primary Outcomes
Safety of treatment as measured by the incidence of grade 3-5 hemoptysis, as assessed by NCI CTCAE version 3.0
Time Frame: Up to 12 months after completion of treatment
All toxicities will be tabulated.
Secondary Outcomes
- Progression-free survival defined as the duration of time from start of protocol treatment to time of progression or death according to RECIST(Up to 2 years)
- Overall survival(Up to 12 months)
- Response rate according to RECIST(Up to 12 months)