A clinical study comparing the effects of chemotherapy plus Avastin to chemotherapy plus Avastin plus a new drug (MEGF0444A) in patients with non-small cell lung cancer who have not received chemotherapy before

• Conditions: ADVANCED OR RECURRENT NON-SQUAMOUS NON-SMALL CELL LUNG CANCER WHO HAVE NOT RECEIVED PRIOR CHEMOTHERAPY FOR ADVANCED DISEASE; MedDRA version: 14.0Level: LLTClassification code 10025054Term: Lung cancer non-small cell stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025052Term: Lung cancer non-small cell stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025048Term: Lung cancer non-small cell recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025051Term: Lung cancer non-small cell stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025046Term: Lung cancer cell type unspecified stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025055Term: Lung cancer non-small cell stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025053Term: Lung cancer non-small cell stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10025050Term: Lung cancer non-small cell stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000711-85-HU
• Lead Sponsor: Genentech, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09-02
• Last Update Posted: 24 June 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Patients must meet the following criteria to be eligible for study entry:
• Signed informed consent form
• Age = 18 years
• Able to comply with the protocol
• Histologically or cytologically documented inoperable (Stage IV) or recurrent non-squamous NSCLC. Diagnoses of non-squamous NSCLC that are based on sputum cytology alone are not acceptable. Mixed tumors should be categorized according to the predominant cell type.
• ECOG performance status of 0 or 1 (see Appendix E)
• Life expectancy >12 weeks
• Measurable disease, as defined by RECIST 1.1 (see Appendix C)
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
Absolute neutrophil count (ANC) = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to randomization)
Platelet count = 100,000/µL (without transfusion within 2 weeks prior to randomization)
Hemoglobin = 9.0 g/dL Patients may be transfused or receive erythropoietic treatment to meet this criterion.
AST, ALT, and alkaline phosphatase = 2.5 × ULN, with the following exceptions:
Patients with documented liver metastases: AST and/or ALT = 5 × ULN
Patients with documented liver or bone metastases:alkaline phosphatase = 5 × ULN, Serum bilirubin <1.5x ULN, Patients with known Gilbert disease who have serum bilirubin level
= 3 × ULN may be enrolled.
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5 × ULN within 7 days prior to starting study treatment
Serum creatinine = 1.5 × ULN or creatinine clearance = 50 mL/min on the basis of the Cockroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)
Urine dipstick for proteinuria < 2+. Patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate = 1 g of protein in 24 hours.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for 6 months after the last dose of bevacizumab or MEGF0444A/placebo
• Negative serum pregnancy test within 7 days of starting study treatment in premenopausal women and women < 2 years after the onset of menopause

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
;
Patients must meet the following criteria to be eligible for study entry:
• Signed informed consent form
• Age = 18 years
• Able to comply with the protocol
• Histologically or cytologically documented inoperable (Stage IV) or recurrent non-squamous NSCLC. Diagnoses of non-squamous NSCLC that are based on sputum cytology alone are not acceptable. Mixed tumors should be categorized according to the predominant cell type.
• ECOG performance status of 0 or 1 (see Appendix E)
• Life expectancy >12 weeks
• Measurable disease, as defined by RECIST 1.1 (see Appendix C)
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
Absolute neutrophil count (ANC) = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to randomization)
Platelet count = 100,000/µL (without transfusion within 2 weeks prior to randomization)
Hemoglobin = 9.0 g/dL Patients may be transfused or receive erythropoietic treatment to meet this criterion.
AST, ALT, and alkaline phosphatase = 2.5 × ULN, with the following exceptions:
Patients with documented liver metastases: AST and/or ALT = 5 × ULN
Patients with documented liver or bone metastases:alkaline phosphatase = 5 × ULN, Serum bilirubin <1.5x ULN, Patients with known Gilbert disease who have serum bilirubin level
= 3 × ULN may be enrolled.
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) = 1.5 × ULN within 7 days prior to starting study treatment
Serum creatinine = 1.5 × ULN or creatinine clearance = 50 mL/min on the basis of the Cockroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)
Urine dipstick for proteinuria < 2+. Patients discovered to have = 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate = 1 g of protein in 24 hours.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for 6 months after the last dose of bevacizumab or MEGF0444A/placebo
• Negative serum pregnancy test within 7 days of starting study treatment in premenopausal women and women < 2 years after the onset of menopause

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study entry:
a. General Medical Exclusions
• Prior therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for the treatment of Stage IV or recurrent NSCLC Patients who received prior adjuvant chemotherapy or radiotherapy for NSCLC are not excluded if the time interval from completion of adjuvant therapy until disease progression is > 12 months.
Patients who received prior palliative radiotherapy for bone metastases
are not excluded (if >1 week prior to Day 1 of Cycle 1).
Patients who receive hormone-replacement therapy or oral contraceptives are not excluded
Patients who received herbal therapy = 2 weeks prior to Day 1 are not excluded
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent
• Symptomatic or uncontrolled hypercalcemia requiring continued use of bisphosphonate therapy
Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinical significant hypercalcemia are eligible.
Uncontrolled hypercalcemia (Ca > 12 mg/dL or >1.5 ionized calcium)
• Pregnant and lactating women
• Known hypersensitivity to Chinese hamster ovary cell products, recombinant human antibodies or any of the chemotherapy agents to be used in this study
• Any disorder that compromises the ability of the patient to provide written informed consent and/or to comply with study procedures
• Leptomeningeal disease
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of = 10 mg/day prednisone
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Grade = 2 peripheral neuropathy
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk for treatment complications

For Bevacizumab-Specific Exclusions please see study protocol
;
Patients who meet any of the following criteria will be excluded from study entry:
a. General Medical Exclusions
• Prior therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for the treatment of Stage IV or recurrent NSCLC Patients who received prior adjuvant chemotherapy or radiotherapy for NSCLC are not excluded if the time interval from completion of adjuvant therapy until disease progression is > 12 months.
Patients who received prior palliative radiotherapy for bone metastases
are not excluded (if >1 week prior to Day 1 of Cycle 1).
Patients who receive hormone-replacement therapy or oral contraceptives are not excluded
Patients who received herbal therapy = 2 weeks prior to Day 1 are not excluded
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Malignancies other than NSCLC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent
• Symptomatic or uncontrolled hypercalcemia requiring continued use of bisphosphonate therapy
Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinical significant hypercalcemia are eligible.
Uncontrolled hypercalcemia (Ca > 12 mg/dL or >1.5 ionized calcium)
• Pregnant and lactating women
• Known hypersensitivity to Chinese hamster ovary cell products, recombinant human antibodies or any of the chemotherapy agents to be used in this study
• Any disorder that compromises the ability of the patient to provide written informed consent and/or to comply with study procedures
• Leptomeningeal disease
• Active infection requiring IV antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of = 10 mg/day prednisone
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
• Grade = 2 peripheral neuropathy
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk for treatment complications

For Bevacizumab-Specific Exclusions please see study protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified