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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-02944 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| ECOG-E3501 | |||
| E3501 | Other Identifier | Eastern Cooperative Oncology Group | |
| E3501 | Other Identifier | CTEP | |
| U10CA021115 | U.S. NIH Grant/Contract | View source |
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This phase II trial is studying how well giving cisplatin and etoposide together with bevacizumab works in treating patients with previously untreated extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or deliver tumor-killing substances to them. Giving chemotherapy with a monoclonal antibody may kill more tumor cells.
PRIMARY OBJECTIVES:
I. To evaluate the combination of PE plus concurrent and sequential bevacizumab with respect to six month progression free survival in patients with previously untreated SCLC.
II. To evaluate the combination of PE plus concurrent and sequential bevacizumab with respect to survival and response rate.
III. To evaluate toxicity in patients with extensive small cell lung cancer, treated with the combination of PE plus concurrent and sequential bevacizumab who have received no prior systemic chemotherapy.
SECONDARY OBJECTIVES:
I. To determine if pre-treatment levels of plasma VEGF predict response to chemotherapy with Etoposide-Cisplatin plus concurrent + sequential bevacizumab.
II. To determine if pre-treatment plasma VEGF is predictive of progression free survival and overall survival in advanced SCLC.
III. To determine whether elevated plasma levels of endothelial cell-specific proteins (VCAM, E-selectin), reflective of chemotherapy or bevacizumab induced endothelial damage, are useful markers in assessing response to Etoposide/Cisplatin plus concurrent + sequential bevacizumab.
IV. To determine whether pre- and post-treatment plasma levels of basic fibroblast growth factor (bFGF) is predictive of progression free survival and overall survival or predictive of response to therapy.
OUTLINE: This is a multicenter study.
Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity.
Patients are followed every 6 weeks for up to 3 years from study entry.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (cisplatin, etoposide, bevacizumab) | Experimental | Chemotherapy: Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Bevacizumab therapy: Beginning concurrently with chemotherapy, patients receive bevacizumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 17 courses (1 year) in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cisplatin | Drug | Given IV |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Alive and Progression-free (PF) at 6 Months | Progression-free survival was defined to be the interval in months from the date of registration to the date of documented disease progression or to death without progression. Patients alive without progression at 6 months were included in the numerator when calculating the progression-free rate. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Overall survival is defined as the time from registration to death or date last known alive. Patients alive at last follow-up are censored. | Assessed every 3 months for 2 years, then every 6 months for 1 year |
| Best Objective Response |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alan Sandler | Eastern Cooperative Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eastern Cooperative Oncology Group | Boston | Massachusetts | 02215 | United States |
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Participants were recruited from ECOG member institutions between June 8, 2004 and August 18, 2006.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cisplatin, Etoposide, Bevacizumab | Cisplatin 60 mg/m2 IV, Etoposide 120 mg/m2 IV, and Bevacizumab 15 mg/kg IV on Day 1, Etoposide 120 mg/m2 IV on days 2 and 3 of a 21-day cycle for 4 cycles. Bevacizumab continued for 1 year or until progression. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| etoposide | Drug | Given IV |
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| bevacizumab | Biological | Given IV |
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| laboratory biomarker analysis | Other | Correlative studies |
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Number of patients with complete or partial response by RECIST criteria. |
| Assessed every 6 weeks |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cisplatin, Etoposide, Bevacizumab | Cisplatin 60 mg/m2 IV, Etoposide 120 mg/m2 IV, and Bevacizumab 15 mg/kg IV on Day 1, Etoposide 120 mg/m2 IV on days 2 and 3 of a 21-day cycle for 4 cycles. Bevacizumab continued for 1 year or until progression. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| 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 | Percentage of Participants Alive and Progression-free (PF) at 6 Months | Progression-free survival was defined to be the interval in months from the date of registration to the date of documented disease progression or to death without progression. Patients alive without progression at 6 months were included in the numerator when calculating the progression-free rate. | Per protocol, the analysis included all eligible, treated patients (n=63). The safety analysis included all treated patients, regardless of eligibility (n=64). | Posted | Mean | 95% Confidence Interval | Percentage of Participants | 6 months |
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| Secondary | Overall Survival | Overall survival is defined as the time from registration to death or date last known alive. Patients alive at last follow-up are censored. | Per protocol, the analysis included all eligible, treated patients | Posted | Median | 95% Confidence Interval | months | Assessed every 3 months for 2 years, then every 6 months for 1 year |
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| Secondary | Best Objective Response | Number of patients with complete or partial response by RECIST criteria. | Per protocol, the analysis included all eligible, treated patients. | Posted | Number | Patients Responding | Assessed every 6 weeks |
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Adverse events were assessed at each treatment visit (approximately every 3 weeks) and through 30 days following the end of treatment
Assessment was done routinely for the safety population, which consisted of all 64 treated patients.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cisplatin, Etoposide, Bevacizumab | Cisplatin 60 mg/m2 IV, Etoposide 120 mg/m2 IV, and Bevacizumab 15 mg/kg IV on Day 1, Etoposide 120 mg/m2 IV on days 2 and 3 of a 21-day cycle for 4 cycles. Bevacizumab continued for 1 year or until progression. | 49 | 64 | 63 | 64 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic Reaction | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
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| Low Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Low Leukocytes | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Low Neutrophils | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Low Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Sinus Bradycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Cardiac ischemia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Left ventricular diastolic dysfunction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Cardiac - other | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Death - multiorgan failure | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Diarrhea w/o prior colostomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Muco/stomatitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Abdomen, hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Bronchopulmonary, hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Febrile Neutropenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Infection w/ gr 3-4 neutrophils, lung | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Infection w/ gr 0-2 neutrophils, lung | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Infection w/ gr 3-4 neutrophils, blood | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Extremity, lower (gait/walking) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Nonneuropathic generalized weakness | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Ataxia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Back, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Bone, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Joint, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Muscle, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Pain, other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Pulmonary/upper respiratory, other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Thrombosis/thrombus/embolism | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Leukocytes | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neutrophils | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
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| Fever w/o neutropenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
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| Insomnia | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Rigors/chills | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Weight loss | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Injection site reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Pruritis/itching | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Diarrhea w/o prior colostomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Muco/stomatitis by exam, oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Muco/stomatitis (symptom), oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Taste disturbance | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nose, hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Alkaline phosphatase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| AST, SGOT | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Proteinuria | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neuropathy, motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Neuropathy, sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Vision - blurred | Eye disorders | CTCAE (3.0) | Systematic Assessment |
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| Back, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Muscle, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Voice changes/dysarthria | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Statistician | ECOG Statistical Office | 617-632-3012 |
| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D005047 | Etoposide |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| 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 |
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