Multimodality Treatment for Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) - BEACON Study: Bevacizumab and Chemotherapy for Operable NSCLC - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center Genentech M.D. Anderson Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00130780

Purpose

This is a phase II, single institution trial for patients with clinical Stage IB-IIIA NSCLC (T1-3N0-2M0) who have resectable lung tumors. The primary goal of this study is to show that the addition of bevacizumab to a cisplatin-based chemotherapy in the neoadjuvant setting for non-squamous cell carcinomas improves the rate of pathologic downstaging, which correlates with survival. Downstaging is defined as any decrease in the final pathologic stage compared with the clinical stage before induction therapy.

Condition	Intervention	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Pre-surgical Treatment with Bevacizumab plus Chemotherapy Drug: Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Docetaxel Cisplatin Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Multimodality Treatment for Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) (BEACON Study: Bevacizumab and Chemotherapy for Operable NSCLC)

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

The primary goal of this study is to show that the addition of bevacizumab to cisplatin-based chemotherapy in the neoadjuvant setting for non-squamous cell carcinomas improves the rate of pathologic downstaging. [ Time Frame: end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the 3-year overall survival and median survival for stage IB-IIIA NSCLC patients treated with cisplatin-based chemotherapy ± bevacizumab (groups A and B combined) [ Time Frame: end of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	August 2005
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Pre-surgical Treatment with Bevacizumab plus Chemotherapy	Drug: Pre-surgical Treatment with Bevacizumab plus Chemotherapy On Cycle 1 Day 1,patient will receive bevacizumab 15 mg/kg. On Cycle 1 Day 15, patients receive docetaxel (75 mg/m2), cisplatin (75 mg/m2). Cycle 2 begins 21 days after administration of docetaxel and cisplatin in Cycle 1. In Cycles 2 thru 3, patients will receive 2 preoperative 21-day cycles of docetaxel (75 mg/m2), cisplatin (75 mg/m2), and bevacizumab (15 mg/kg), all given on Day 1 of each cycle. The sequence of administration will be docetaxel, followed by cisplatin, followed by bevacizumab according to MSKCC Chemotherapy Guidelines. In Cycle 4 Day 1, patients will receive docetaxel (75 mg/m2) and cisplatin (75 mg/m2). Bevacizumab will not be given with Cycle 4. During Cycle 4, the only scheduled clinic visit will be on Day 1. Surgery will occur at least 42 days after the last treatment with bevacizumab.
B: Active Comparator Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab	Drug: Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab Patients will receive preoperative 21-day cycles of cisplatin (75 mg/m2) and docetaxel (75 mg/m2) both given on Day 1 of each cycle.Patients will undergo repeat CT imaging after 2 cycles of therapy and patients with at least 10% reduction in bidimensional tumor volume will receive 2 additional neoadjuvant cycles of therapy (total 4 cycles of therapy).Surgery will occur at least 4 weeks after the last treatment with docetaxel and cisplatin.Adjuvant bevacizumab (15 mg/kg q21 days for 1 year, total 18 cycles) will be administered to all patients who undergo resection. Adjuvant bevacizumab will begin between days 42 and 56 after surgery.Patients may be referred for post-operative radiation therapy at the discretion of the treating physician

Arms

Assigned Interventions

A: Active Comparator

Pre-surgical Treatment with Bevacizumab plus Chemotherapy

Drug: Pre-surgical Treatment with Bevacizumab plus Chemotherapy

On Cycle 1 Day 1,patient will receive bevacizumab 15 mg/kg. On Cycle 1 Day 15, patients receive docetaxel (75 mg/m2), cisplatin (75 mg/m2). Cycle 2 begins 21 days after administration of docetaxel and cisplatin in Cycle 1. In Cycles 2 thru 3, patients will receive 2 preoperative 21-day cycles of docetaxel (75 mg/m2), cisplatin (75 mg/m2), and bevacizumab (15 mg/kg), all given on Day 1 of each cycle. The sequence of administration will be docetaxel, followed by cisplatin, followed by bevacizumab according to MSKCC Chemotherapy Guidelines. In Cycle 4 Day 1, patients will receive docetaxel (75 mg/m2) and cisplatin (75 mg/m2). Bevacizumab will not be given with Cycle 4. During Cycle 4, the only scheduled clinic visit will be on Day 1. Surgery will occur at least 42 days after the last treatment with bevacizumab.

B: Active Comparator

Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab

Drug: Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab

Patients will receive preoperative 21-day cycles of cisplatin (75 mg/m2) and docetaxel (75 mg/m2) both given on Day 1 of each cycle.Patients will undergo repeat CT imaging after 2 cycles of therapy and patients with at least 10% reduction in bidimensional tumor volume will receive 2 additional neoadjuvant cycles of therapy (total 4 cycles of therapy).Surgery will occur at least 4 weeks after the last treatment with docetaxel and cisplatin.Adjuvant bevacizumab (15 mg/kg q21 days for 1 year, total 18 cycles) will be administered to all patients who undergo resection. Adjuvant bevacizumab will begin between days 42 and 56 after surgery.Patients may be referred for post-operative radiation therapy at the discretion of the treating physician

Detailed Description:

Primary Objective:

To determine the rate of downstaging for Stage IB-IIIA NSCLC patients treated with neoadjuvant chemotherapy + bevacizumab (group A only; non-squamous cell). Downstaging is defined as any decrease in the final pathologic stage compared with the clinical stage before induction therapy.

Secondary Objectives:

To determine the 3-year overall survival and median survival for stage IB-IIIA NSCLC patients treated with cisplatin-based chemotherapy ± bevacizumab (groups A and B combined).
For patients with stage IB-IIIA NSCLC, to determine the safety profiles of preoperative bevacizumab + chemotherapy and postoperative bevacizumab monotherapy.
To explore potential surrogate markers of bevacizumab activity, including levels of VEGF-A (in plasma and in platelets), endothelial progenitor cells (EPCs), and hematopoietic progenitor cells (HPCs).
In pre and post-treatment tumor samples, to evaluate expression of VEGF receptors 1, 2, 3 and cognate ligands and explore the relationships with downstaging, objective response rate, and survival.
To explore if radiologic response to bevacizumab can be detected by 3-D volumetric CT scan.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pathologic confirmation of NSCLC at Memorial Sloan-Kettering Cancer Center (MSKCC)
Stages IB, IIA, IIB or IIIA (T1-3N0-2M 0) NSCLC
Patients must be candidates for resection with curative intent.
Measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions
Age >= 18 years
Karnofsky performance status >= 70%
Normal marrow function: leukocytes >= 3,000/µl; absolute neutrophil count ≥ 1,500µl; platelets >= 100,000 µl; hemoglobin >= 9gm/dl.
Adequate renal function, with creatinine <= 1.3 mg/dl or calculated creatinine clearance >= 60ml/min by Cockcroft-Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl)
Adequate hepatic function: total bilirubin within normal limits; AST <= 1.5 X upper limit of normal (UNL); ALT <= 1.5 X UNL; alkaline phosphatase <= 1.5 X UNL.
Women of childbearing age must have a negative urine or blood pregnancy test.
Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
Patients must have ability to understand and the willingness to sign a written informed consent document.
For group B: patients with squamous cell carcinoma or non-squamous cell large central tumor in proximity to blood vessels will be assigned to group B (preoperative chemotherapy).
Patients with gross hemoptysis (defined as bright red blood of ½ teaspoon or more) within 28 days prior to Day 0 of protocol treatment will now be allowed on protocol Arm B given they will not be receiving bevacizumab until post-operatively.

Exclusion Criteria:

Prior chemotherapy or radiation therapy, with the exception of chemotherapy for non-oncologic conditions (ie, methotrexate for the treatment of rheumatoid arthritis)
Prior treatment with bevacizumab or other agents specifically targeting vascular endothelial growth factor (VEGF)
Patients with a history of severe hypersensitivity reaction to docetaxel (Taxotere) or other drugs formulated with polysorbate 80
Patients with known hypersensitivity to other recombinant human antibodies
Patients must not be receiving any other investigational agents.
Prior malignancy in the past 5 years, other than non-melanoma skin cancer and in situ carcinoma of the cervix
Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher)
Peripheral neuropathy > grade 1.
Uncontrolled hypertension
History of arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI) within the last 3 years.
Patients with clinically significant peripheral arterial disease
Urine protein: creatinine ratio >= 1.0 at screening
History of thrombotic disorders or coagulopathy
History of bleeding diathesis or hemorrhagic disorders.
Patients must have International Normalized Ratio (INR) <= 1.5 and a partial thromboplastin time (PTT) <=1.5 X upper limit of normal (UNL).
Current use of warfarin.
Current use of heparin or low-molecular weight heparin.
Chronic daily treatment with aspirin (> 81mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function. Treatment with dipyramidole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and or cilostazol (Pletal) is also not allowed.
Esophageal varices, non-healing ulcer, wound, or bone fracture
Significant traumatic injury or major surgery within 28 days prior to Day 0 of protocol treatment
For group A: Patients with Squamous Cell carcinoma or Non-Squamous Cell large central tumor in proximity to significant blood vessels or patients with history of gross hemoptysis (defined as bright red blood of ½ teaspoon of more) within 28 days prior to Day 0 protocol treatment will be excluded from group A (preoperative chemotherapy plus bevacizumab); these patients will be assigned to group B (preoperative chemotherapy).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130780

Contacts

Contact: Naiyer Rizvi, M.D.

212-639-3204

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Naiyer Rizvi, MD rizvin@mskcc.org
Principal Investigator: Naiyer Rizvi, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Genentech

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Naiyer Rizvi, M.D.

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan Kettering Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan Kettering Cancer Center ( Naiyer Rizvi, MD )
Study ID Numbers:	05-052
Study First Received:	August 12, 2005
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00130780
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Multi-modality treatment for lung cancer
Carcinoma, Squamous Cell

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Bevacizumab
Carcinoma
Docetaxel
Respiratory Tract Diseases
Cisplatin

Lung Neoplasms
Lung Diseases
Carcinoma, squamous cell
Carcinoma, Squamous Cell
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009