A Phase II Study of Neo-Adjuvant Gemcitabine, Cisplatin and Bevacizumab in Stage IIIA (N2) Non-Squamous Cell Non-Small Cell Lung Cancer
This study has been terminated.
(Study was terminated due to poor accrual.)
Information provided by (Responsible Party):
Giuseppe Giaccone, National Institutes of Health Clinical Center (CC)
First received: June 17, 2009
Last updated: August 21, 2012
Last verified: August 2012
- Surgical resection is the treatment of choice for patients with lung cancer, and cure after resection generally depends on whether lymph nodes are involved. A patient with Stage IIIA (N2) lung cancer has cancer in the lymph nodes involving the center of the chest (mediastinum).
- Studies have shown that surgery alone as a treatment for Stage IIIA (N2) lung cancer is not as effective as chemotherapy followed by surgery.
- Giving chemotherapy upfront may prevent the spread of Stage IIIA (N2) lung cancer tumors, and may shrink the tumors to allow adequate surgery to be performed. It is also thought that chemotherapy is usually better tolerated before major surgery than after, so higher doses can be given.
- To determine the effectiveness of the combination of three anti-cancer drugs (gemcitabine, cisplatin, and bevacizumab) given before surgery.
- To find out what effects this drug combination may have on the patient and the cancer.
- To determine if the combination of all three drugs given prior to surgery is more effective and as safe, safer, or less safe than other drug combinations given before surgery.
- Patients with Stage IIIA (N2) lung cancer who have not had chemotherapy, radiation, or surgery to treat the cancer.
- Evaluations before the treatment period to determine eligibility:
- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Tests to evaluate heart and lung function, such as an echocardiogram.
- Blood and urine tests.
- Disease evaluation with computed tomography (CT), chest X-ray, positron emission tomography (PET) scans, and bronchoscopy/mediastinoscopy (examinations of the inside of the chest and lungs).
- Treatment with intravenous gemcitabine, cisplatin, and bevacizumab for three 21-day cycles.
- Cycles 1 and 2 - Gemcitabine on day 1 and day 8, cisplatin on day 1, bevacizumab on day 1.
- Cycle 3 - Gemcitabine on day 1 and day 8, cisplatin on day 1 (no bevacizumab).
- Physical examinations and tests will be conducted throughout each cycle.
- Surgery will take place 4 to 6 weeks after the last cycle if heart and lung functions are satisfactory and if the cancer remains stable.
- Chemotherapy (four 21-day cycles of cisplatin and etoposide treatments), further evaluations and examinations, and followup studies will take place 4 to 8 weeks after the surgery.
Stage IIIA (N2)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Neoadjuvant Gemcitabine, Cisplatin and Bevacizumab in Stage IIIA (N2), Non-Squamous Cell Non-Small Cell Lung Cancer|
Resource links provided by NLM:
Drug Information available for: Cisplatin Etoposide Gemcitabine Etoposide phosphate Gemcitabine hydrochloride BevacizumabU.S. FDA Resources
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Rate of Pathologic Complete Response [ Time Frame: 25 weeks ] [ Designated as safety issue: No ]Complete response is defined as a disappearance of all target lesions and was assessed by the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.
Secondary Outcome Measures:
- Number of Participants With Adverse Events [ Time Frame: 38 months ] [ Designated as safety issue: Yes ]Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
|Study Start Date:||March 2009|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Experimental: Stage IIIA lung cancer patients
Non-squamous cell non small cell lung cancer treated with 1250 mg/m^2 gemcitabine dose for two doses on day 1 and day 8 every 21 days,80 mg/m^2 cisplatin day 1 every 21 days for 3 cycles, 7.5 mg/kg bevacizumab on day 1 every 21 days for first 2 cycles only, and 100 mg/m^2 intravenous, and 100 mg/m^2 etoposide intravenous per day for consecutive 3 days on days 1 to 3 every 3 weeks for 4 cycles.
1250 mg/m^2 dose for two doses on days 1 and 8
Other Name: GemzarDrug: Cisplatin
80 mg/m^2 on day 1
Other Name: CisplatinumDrug: Bevacizumab
7.5 mg/m^2 on day 1 every 21 days for first two cycles only
Other Name: AvastinProcedure: Surgery
thoracotomy with lobectomy/pneumonectomy and mediastinal lymph node dissection 4-6 weeks post completion of last cycle of cisplatinDrug: Etoposide
100 mg/m^2 intravenous per day for consecutive 3 days on days 1 to 3 every 3 weeks for 4 cycles.
Other Name: Vepesid
- Stage IIIA-N2 is considered one of the most therapeutically challenging and controversial subsets of lung cancer. This heterogenous group of patients have tumors which range from minimal N2 (found incidentally during or after surgery) to multi-station bulky N2 disease. The extent of mediastinal involvement has an inverse correlation with survival.
- The 5-year survival ranges from 5-8% in patients with bulky N2 disease, to nearly 35% in patients with single station, microscopic N2 involvement.
- Neo-adjuvant chemotherapy and chemo-radiotherapy have been shown to be superior to surgery alone.
- Platinum-based induction chemotherapy in early and locally advanced non small cell lung cancer (NSCLC) results in a radiological down-staging in at least 50% of patients, and a pathological complete response rate of approximately 5%.
- Concurrent chemo-radiotherapy as an induction regimen increases the radiological and pathological down-staging rate, but at the cost of increasing the morbidity and mortality of a surgical intervention.
- Expectations have now turned towards a possible incremental effect of adding a targeted biological agent to a standard induction treatment.
- To determine the safety of neo-adjuvant Gemcitabine/Cisplatin and Bevacizumab in stage IIIA-N2 non small cell lung cancer (NSCLC)
- To determine the pathological complete response rate
- To determine the resectability rate
- To determine the extent of surgery
- Histologically confirmed stage IIIA-N2 NSCLC (non-squamous)
- No previous chemotherapy, radiotherapy, surgery or biological therapy for lung cancer
- Adequate organ and bone marrow function
- Multi-center, international (United States Of America (USA)/Croatia), open labeled phase II trial
- Following a Simon two-stage optimal design
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00924209
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|University Hospital for Lung Diseases|
Sponsors and Collaborators
|Principal Investigator:||Giuseppe Giaccone, M.D.||National Cancer Institute, National Institutes of Health|