Multimodality Treatment for Patients With Resectable Non-... | NCT00130780

NCT00130780

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A	Active Comparator	Pre-surgical Treatment with Bevacizumab plus Chemotherapy	Drug: Pre-surgical Treatment with Bevacizumab plus Chemotherapy
B	Active Comparator	Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab	Drug: Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pre-surgical Treatment with Bevacizumab plus Chemotherapy	Drug	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. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally 2 weeks after it is scheduled, if necessary.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Therapeutic Response/Outcome Assessment.	These criteria have been modified for the purpose of this study (i.e.: there will be no confirmation of response at 4 weeks per usual response criteria as this is not applicable to the preoperative treatment plan): Complete Response (CR): Disappearance of all clinical evidence of tumor. Partial Response (PR): A 50% or greater decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Minor Response (MR): A > 25% and < 50% decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Stable Disease (SD): A less than 25% decrease. This includes a decrease of less than 25% in the sum of the products of the meas	2 years

Eligibility Module

Eligibility 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.
Eligibility criteria for group B: Patients with SQUAMOUS CELL carcinoma or patients with a NON-SQUAMOUS CELL tumor with a large central tumor in proximity to significant blood vessels or any history of hemoptysis will be assigned to group B (preoperative chemotherapy alone without bevacizumab).

Exclusion Criteria:

Prior chemotherapy or radiation therapy for NSCLC
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.
History of stroke or transient ischemic attack (TIA).
History of myocardial infarction or unstable angina within the past 12 months.
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
Esophageal varices, non-healing ulcer, wound, or bone fracture
Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs.
Other serious illness or medical condition including unstable cardiac disease requiring treatment, history of significant neurologic or psychiatric disorders (including psychotic disorders, dementia, or seizures), symptomatic diverticulitis, or active uncontrolled infection.
Women who are pregnant or breast-feeding
Psychiatric illness or social situation that would limit compliance with study requirements
Exclusion criteria for group A: Patients with SQUAMOUS CELL carcinoma, large central tumor in proximity to significant blood vessels, or any history of hemoptysis (will be excluded from group A (preoperative chemotherapy plus bevacizumab); these patients will be assigned to group B (preoperative chemotherapy).

Name	Affiliation	Role
Naiyer Rizvi, M.D.	Memorial Sloan Kettering Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Memorial Sloan Kettering Cancer Center		New York	New York	10021	United States

Label	URL
Memorial Sloan Kettering Cancer Center	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	A: Pre-surgical Treatment With Bevacizumab Plus Chemotherapy	Pre-surgical Treatment with Bevacizumab plus Chemotherapy Pre-surgical Treatment with Bevacizumab + 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. Every attempt will be made to administer the treatment on sc

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	A: Pre-surgical Treatment With Bevacizumab Plus Chemotherapy	Pre-surgical Treatment with Bevacizumab plus Chemotherapy Pre-surgical Treatment with Bevacizumab + 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. Every attempt will be made to administer the treatment on sc
BG001	B: Pre-Surgical Docetaxel, Cisplatin, and Adjuvant Bevacizumab	Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab 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. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00051 BG00120 BG00271

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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 Therapeutic Response/Outcome Assessment.

These criteria have been modified for the purpose of this study (i.e.: there will be no confirmation of response at 4 weeks per usual response criteria as this is not applicable to the preoperative treatment plan): Complete Response (CR): Disappearance of all clinical evidence of tumor. Partial Response (PR): A 50% or greater decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Minor Response (MR): A > 25% and < 50% decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Stable Disease (SD): A less than 25% decrease. This includes a decrease of less than 25% in the sum of the products of the meas

Posted

Number

participants

2 years

ID	Title	Description
OG000	A: Pre-surgical Treatment With Bevacizumab Plus Chemotherapy	Pre-surgical Treatment with Bevacizumab plus Chemotherapy Pre-surgical Treatment with Bevacizumab + 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. Every attempt will be made to administer the treatment on sc
OG001	B: Pre-Surgical Docetaxel, Cisplatin, and Adjuvant Bevacizumab	Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab 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. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally

Units	Counts
Participants	OG00051 OG00120

Title

Denominators

Categories

Title	Measurements
	OG00051 OG00120

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A: Pre-surgical Treatment With Bevacizumab Plus Chemotherapy	Pre-surgical Treatment with Bevacizumab plus Chemotherapy Pre-surgical Treatment with Bevacizumab + 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. Every attempt will be made to administer the treatment on sc			28	51	49	51
EG001	B: Pre-Surgical Docetaxel, Cisplatin, and Adjuvant Bevacizumab	Pre-Surgical Docetaxel and Cisplatin and Adjuvant Bevacizumab 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. Every attempt will be made to administer the treatment on schedule. The treatment may be given +/- 3 days, and additionally			6	20	19	20

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Dehydration	Gastrointestinal disorders	Systematic Assessment	EG0005 events4 affected51 at risk EG0011 events1 affected20 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Dyspnea (shortness of breath)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 events5 affected51 at risk EG0010 events0 affected20 at risk
Enteritis (inflamm of small bowel)	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Fatigue (asthenia, lethargy, malaise)	General disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0004 events4 affected51 at risk EG0011 events1 affected20 at risk
Mucositis (Clin exam)- Oral cavity	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Neutrophils/granulocytes (ANC/AGC)	Investigations	Systematic Assessment	EG0004 events4 affected51 at risk EG0012 events2 affected20 at risk
Pain - Chest/thorax NOS	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 events2 affected51 at risk EG0010 events0 affected20 at risk
Syncope (fainting)	Nervous system disorders	Systematic Assessment	EG0000 events0 affected51 at risk EG0013 events2 affected20 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
ALT, SGPT	Metabolism and nutrition disorders	Systematic Assessment	EG0006 events1 affected51 at risk EG00110 events3 affected20 at risk
Albumin, low (hypoalbuminemia)	Metabolism and nutrition disorders	Systematic Assessment	EG00054 events18 affected51 at risk EG0018 events3 affected20 at risk
Bilirubin (hyperbilirubinemia)	Investigations	Systematic Assessment	EG00017 events3 affected51 at risk EG0012 events1 affected20 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG00013 events9 affected51 at risk EG0014 events1 affected20 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00011 events5 affected51 at risk EG0014 events2 affected20 at risk
Creatinine	Investigations	Systematic Assessment	EG00010 events4 affected51 at risk EG0012 events2 affected20 at risk
Dehydration	Gastrointestinal disorders	Systematic Assessment	EG0004 events2 affected51 at risk EG0011 events1 affected20 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG00014 events10 affected51 at risk EG0016 events3 affected20 at risk
Dyspnea (shortness of breath)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0008 events5 affected51 at risk EG0012 events1 affected20 at risk
Fatigue (asthenia, lethargy, malaise)	General disorders	Systematic Assessment	EG000106 events34 affected51 at risk EG00120 events9 affected20 at risk
Glucose, high (hyperglycemia)	Metabolism and nutrition disorders	Systematic Assessment	EG00090 events40 affected51 at risk EG00141 events15 affected20 at risk
Hair loss/alopecia (scalp or body)	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00018 events13 affected51 at risk EG0016 events3 affected20 at risk
Hemoglobin	Blood and lymphatic system disorders	Systematic Assessment	EG00079 events35 affected51 at risk EG00122 events11 affected20 at risk
Hypertension	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0006 events4 affected51 at risk EG0010 events0 affected20 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG00023 events15 affected51 at risk EG0016 events4 affected20 at risk
Lymphopenia	Investigations	Systematic Assessment	EG00021 events15 affected51 at risk EG00114 events7 affected20 at risk
Magnesium, low (hypomagnesemia)	Metabolism and nutrition disorders	Systematic Assessment	EG00012 events8 affected51 at risk EG0013 events2 affected20 at risk
Mucositis (Clin exam)- Oral cavity	Gastrointestinal disorders	Systematic Assessment	EG00029 events12 affected51 at risk EG0015 events4 affected20 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00032 events13 affected51 at risk EG0016 events2 affected20 at risk
Neutrophils/granulocytes (ANC/AGC)	Investigations	Systematic Assessment	EG00026 events20 affected51 at risk EG0014 events4 affected20 at risk
Phosphate, low (hypophosphatemia)	Metabolism and nutrition disorders	Systematic Assessment	EG00014 events13 affected51 at risk EG0016 events6 affected20 at risk
Platelets	Investigations	Systematic Assessment	EG0008 events5 affected51 at risk EG0010 events0 affected20 at risk
Potassium, high (hyperkalemia)	Metabolism and nutrition disorders	Systematic Assessment	EG00010 events7 affected51 at risk EG0010 events0 affected20 at risk
Potassium, low (hypokalemia)	Investigations	Systematic Assessment	EG0003 events3 affected51 at risk EG0010 events0 affected20 at risk
Sodium, low (hyponatremia)	Metabolism and nutrition disorders	Systematic Assessment	EG00012 events9 affected51 at risk EG0012 events2 affected20 at risk
Tinnitus	Ear and labyrinth disorders	Systematic Assessment	EG00019 events12 affected51 at risk EG0019 events4 affected20 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D002294	Carcinoma, Squamous Cell

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D018307	Neoplasms, Squamous Cell

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D013812	Therapeutics
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds

ID	Term
D000068258	Bevacizumab
D004358	Drug Therapy
D002945	Cisplatin