A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-small Cell Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Lung Adenocarcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 29
- Locations
- 63
- Primary Endpoint
- Adverse Events
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This clinical trial studies combination chemotherapy, radiation therapy, and bevacizumab in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as cisplatin, etoposide, and docetaxel, work in different ways to stop the growth of [cancer/tumor] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with radiation therapy and bevacizumab may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the frequency and severity of toxic effects of induction therapy comprising cisplatin, etoposide, and radiotherapy with or without bevacizumab followed by consolidation therapy comprising docetaxel and bevacizumab, in terms of grade 4 or 5 hemorrhage, in patients with newly diagnosed, unresectable, stage III non-small cell lung cancer. SECONDARY OBJECTIVES: I. Determine progression-free and overall survival of patients treated with these regimens. II. Determine response (confirmed, unconfirmed, partial, and complete) in patients with measurable disease treated with these regimens. OUTLINE: This is a pilot, multicenter study. Patients are stratified according to risk (high\* vs low). NOTE: \*High-risk stratum closed to accrual as of 2/20/09. INDUCTION THERAPY: Patients in each stratum are assigned to 1 of 3 sequential treatment groups. GROUP 1: Patients receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. GROUP 2: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57. GROUP 3: Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43. CONSOLIDATION CHEMOTHERAPY: Beginning 3-6 weeks after completion of induction therapy, all patients receive consolidation chemotherapy comprising docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 2 and continuing until blood counts recover OR pegfilgrastim SC once on day 2. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 4 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed single, primary, bronchogenic, non-small cell lung cancer (NSCLC)
- •Newly diagnosed disease
- •Unresectable disease
- •No more than 1 parenchymal lesions on same or opposite sides of the lungs
- •Meets 1 of the following stage criteria:
- •Stage IIIA (N2) disease meeting the following criteria:
- •N2 mediastinal lymph nodes must be multiple and/or bulky on CT scan or x-ray so that the patient is not a candidate for induction chemotherapy or chemoradiotherapy followed by surgical resection
- •N2 status must be documented by ≥ 1 of the following methods:
- •Histologically or cytologically confirmed N2 disease by exploratory thoracotomy, thoracoscopy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle biopsy (WNB), fine needle aspiration (FNA) under bronchoscopic or CT guidance, or any other method
- •Node positive by fludeoxyglucose-positron emission tomography (FDG-PET) scan
Exclusion Criteria
- Not provided
Arms & Interventions
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Docetaxel
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Etoposide
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Cisplatin
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Filgrastim
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Pegfilgrastim
Group 1 (cisplatin, etoposide, radiotherapy)
Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Patients undergo concurrent thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47.
Intervention: Radiation Therapy
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Bevacizumab
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Cisplatin
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Docetaxel
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Etoposide
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Filgrastim
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Pegfilgrastim
Group 2 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 15, 36, and 57.
Intervention: Radiation Therapy
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Bevacizumab
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Cisplatin
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Docetaxel
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Etoposide
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Filgrastim
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Pegfilgrastim
Group 3 (cisplatin, etoposide, radiotherapy, bevacizumab)
Patients receive cisplatin, etoposide, and thoracic radiotherapy as in group 1. Patients also receive bevacizumab IV over 30-90 minutes on days 1, 22, and 43.
Intervention: Radiation Therapy
Outcomes
Primary Outcomes
Adverse Events
Time Frame: Up to one year
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Secondary Outcomes
- Progression-free Survival(Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.)
- Response Rate (Confirmed or Unconfirmed Partial Response)(Response assessment occured at the end of CRT and docetaxel/bevacizumab and then every 2-3 months for 2 years and then every 6 months until 4 years after the initial registration)
- Overall Survival(Every week, up to 4 years)