Transarterial Chemoperfusion: Cisplatin, Methotrexate, Ge... | NCT02611037

Label	Type	Description	Intervention Names
Chemoperfusion + Questionnaire	Experimental	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.	Drug: Cisplatin Drug: Methotrexate Drug: Gemcitabine Other: Lung Cancer Symptom Scale for Mesothelioma Questionnaire

Name	Type	Description	Arm Group Labels	Other Names
Cisplatin	Drug	The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin.

Measure	Description	Time Frame
Disease Control Rate (DCR)	Disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine in patients with unresectable malignant pleural mesothelioma using modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. DCR provided as percentage of participants with partial response + percentage of participants with stable disease.	Up to 3 years

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival defined as the time from the first day of transarterial chemoperfusion treatment to death.	Up to 3 years
Progression Free Survival (PFS)	Progression free survival defined as the time from the first day of transarterial chemoperfusion treatment to disease progression based on imaging findings using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for mesothelioma. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Must have histologically or cytologically confirmed malignant pleural mesothelioma (MPM).
Have unresectable MPM or the patient refuses surgery for resectable MPM.
Have failed to respond first line standard of care chemotherapy or the patient refuses first line chemotherapy.
Have measurable disease, by computed tomography (CT) or magnetic resonance imaging (MRI) per modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. Radiographic tumor assessment must be performed within 28 days prior to the first treatment.
The predominant burden of disease lies in an arterial distribution which is accessible for transarterial chemoperfusion treatment.
Eastern Cooperative Oncology Group (ECOG) performance status <2 (Karnofsky >60%).
All baseline laboratory requirements will be assessed and should be obtained within 14 days of first treatment. Screening laboratory values must be met..
Women participate in the study must be surgically sterile, post-menopausal, or women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation and after for a certain amount of time (up to 5 weeks) after the last treatment.
Women must have a negative serum or urine pregnancy test within 24 hours prior to the start of transarterial chemoperfusion treatment.
Men must be surgically sterile or must agree to use adequate contraception prior to study entry and for the duration of study participation and after for a certain amount of time (up to 14 weeks) after the last treatment.
Ability to understand and the willingness to sign a written informed consent document.
Participants must have signed and dated an Institutional Review Board (IRB) approved written informed consent form in accordance with regulatory and institutional guidelines.
Must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, imaging studies, and other requirements of the study.
This study permits the re-enrollment of a participant who has discontinued the study for a reason other than treatment failure or adverse event(s) of the study treatment.

Exclusion Criteria:

Patients who have had chemotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Recovery means resolution to at least Grade 1 toxicity if there was no baseline toxicity or less than or equal to the patient's baseline value.
May not be receiving any other investigational agents.
Known brain metastases or leptomeningeal metastases. Patients with other extrapleural metastases are included in this study.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, methotrexate, gemcitabine or other agents used during the study. History of allergic reaction to intravenous iodinated contrast media is not contraindication to the study. Patients with history of mild allergic reaction to iodinated contrast media will be premedicated with 40 mg of prednisone by mouth (p.o.) 12 and 2 hrs before the transarterial chemoperfusion treatment to prevent allergic reaction. Patients with history of moderate and severe allergic reaction to iodinated contrast media or patients with history of mild allergic reaction to iodinated contrast media despite adequate premedication will undergo angiogram using carbon dioxide or a gadolinium based contrast agent.
Uncontrolled intercurrent illness including, but not limited to, presence of other malignancy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Women who are pregnant or breastfeeding.
HIV-positive patients receiving combination anti-retroviral therapy.
Potential participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.

Name	Affiliation	Role
Bela Kis, M.D., Ph.D.	H. Lee Moffitt Cancer Center and Research Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
H. Lee Moffitt Cancer Center and Research Institute		Tampa	Florida	22612	United States

Label	URL
Moffitt Cancer Center Clinical Trials website	View source

ID	Title	Description
FG000	Chemoperfusion -Lead In	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 27, 2018

ID	Title	Description
BG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

Units	Counts
Participants	BG00034

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

Disease Control Rate (DCR)

Disease control rate of transarterial chemoperfusion treatment with cisplatin, methotrexate and gemcitabine in patients with unresectable malignant pleural mesothelioma using modified Response Evaluation Criteria in Solid Tumors (RECIST) for mesothelioma. DCR provided as percentage of participants with partial response + percentage of participants with stable disease.

All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.

Posted

Number

percentage of participants

Up to 3 years

ID	Title	Description
OG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

Units	Counts
Participants	OG00032

Title

Denominators

Categories

Title	Measurements
	OG00075

Secondary

Overall Survival (OS)

Overall survival defined as the time from the first day of transarterial chemoperfusion treatment to death.

All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.

Posted

Median

95% Confidence Interval

months

Up to 3 years

ID	Title	Description
OG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

Secondary

Progression Free Survival (PFS)

Progression free survival defined as the time from the first day of transarterial chemoperfusion treatment to disease progression based on imaging findings using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for mesothelioma. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.

Posted

Median

95% Confidence Interval

months

Up to 3 years

ID	Title	Description
OG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

Secondary

Occurrence of Treatment Related Toxicity

Safety was assessed by monitoring adverse events and serious adverse events; the association with study treatment was assessed, and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. Number of events that were Possible, Probable or Definitely related to study treatment.

All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.

Posted

Number

related adverse events

Up to 3 years

ID	Title	Description
OG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

Secondary

Quality of Life Questionnaire Scores

Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Mesothelioma Symptom Scale includes 7 categories to rate on a scale of 1 to 10 regarding severity of symptoms during the last 24 hours. A higher number indicates more severe symptoms.

Quality of life questionnaires were not collected, therefore this measure cannot be analyzed.

Posted

Up to 3 years

ID	Title	Description
OG000	Chemoperfusion + Questionnaire	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine. Lung Cancer Symptom Scale for Mesothelioma Questionnaire: Quality of life will be assessed using the modified version of the Lung Cancer Symptom Scale for Mesothelioma questionnaire.

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	Chemoperfusion - Lead In	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). During the lead in phase of the study, 3 patients will be treated with regular doses of cisplatin. Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with 50% reduced dose of methotrexate (50 mg/m^2). Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA. During the lead in phase of the study, 3 patients will be treated with regular doses of gemcitabine.	2	5	2	5	5	5
EG001	Chemoperfusion - Open Label	Transarterial Chemoperfusion treatment with cisplatin (35 mg/m^2), methotrexate (100 mg/m^2) and gemcitabine (1000 mg/m^2). Patients undergo angiogram and transarterial chemoperfusion treatment in every 4 weeks (3-6 weeks interval allowed) when cisplatin, methotrexate and gemcitabine will be administered into the thoracic aorta and/or the internal mammary artery on the side of the disease. Cisplatin: The recommended dose of cisplatin for transarterial chemoperfusion in this study is 35 mg/m^2 body surface area (BSA). Methotrexate: The recommended dose of methotrexate for transarterial chemoperfusion in this study is 100 mg/m^2 BSA. Gemcitabine: The recommended dose of gemcitabine for transarterial chemoperfusion in this study is 1000 mg/m^2 BSA	21	25	7	25	25	25

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0012 events2 affected25 at risk
Fatigue	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0003 events1 affected5 at risk EG0010 events0 affected25 at risk
Dyspena	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0005 events2 affected5 at risk EG0011 events1 affected25 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0013 events1 affected25 at risk
Edema limbs	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Urinary tract infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected25 at risk
Thromboembolic event	Vascular disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Fever	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Esophageal perforation	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected25 at risk
Stroke	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Lung infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected25 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Vomiting	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Upper respiratory infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Non-cardiac chest pain	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chest wall pain	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG00011 events4 affected5 at risk EG00146 events16 affected25 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0016 events5 affected25 at risk
Back Pain	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events3 affected25 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events1 affected25 at risk
Flank pain	Musculoskeletal and connective tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0008 events2 affected5 at risk EG00133 events12 affected25 at risk
Hyperkalemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0007 events5 affected5 at risk EG00110 events8 affected25 at risk
Hyponatremia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0004 events3 affected5 at risk EG00112 events4 affected25 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0003 events3 affected5 at risk EG0018 events3 affected25 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0014 events4 affected25 at risk
Hypercalcemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0003 events2 affected5 at risk EG0013 events3 affected25 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected25 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0013 events2 affected25 at risk
Hypernatremia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected25 at risk
Dehydration	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Hypermagnesemia	Metabolism and nutrition disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected25 at risk
Anemia	Blood and lymphatic system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0007 events3 affected5 at risk EG00134 events12 affected25 at risk
Leukocytosis	Blood and lymphatic system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0015 events4 affected25 at risk
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Nausea	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0005 events3 affected5 at risk EG00126 events12 affected25 at risk
Vomiting	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0018 events8 affected25 at risk
Constipation	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events5 affected25 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events5 affected25 at risk
Dysphagia	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Esophageal perforation	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Stomach pain	Gastrointestinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Lymphocyte count decreased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0006 events3 affected5 at risk EG00113 events7 affected25 at risk
Creatinine increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG00112 events5 affected25 at risk
INR increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0002 events2 affected5 at risk EG0016 events2 affected25 at risk
Alanine aminotransferase increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0013 events2 affected25 at risk
Alkaline phosphatase increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0013 events2 affected25 at risk
White blood cell decreased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events2 affected25 at risk
Activated partial thromboplastin time prolonged	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0016 events1 affected25 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Blood bilirubin increased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Ejection fraction decreased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Neutrophil count decreased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events1 affected25 at risk
Platelet count decreased	Investigations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Fatigue	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG00112 events8 affected25 at risk
Pain	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0014 events4 affected25 at risk
Fever	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Flu-like symptoms	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events2 affected25 at risk
Non-cardiac chest pain	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Edema limbs	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
General disorders and administration site conditions - Other	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Infusion related reaction	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0003 events1 affected5 at risk EG0010 events0 affected25 at risk
Localized edema	General disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0004 events2 affected5 at risk EG0017 events7 affected25 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events3 affected25 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0003 events1 affected5 at risk EG0015 events2 affected25 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected25 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Postnasal drip	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Respiratory, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0002 events1 affected5 at risk EG0010 events0 affected25 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Dizziness	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0015 events4 affected25 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events3 affected25 at risk
Paresthesia	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Headache	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Peripheral motor neuropathy	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Presyncope	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Stroke	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Syncope	Nervous system disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Upper respiratory infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events3 affected25 at risk
Infections and infestations - Other	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Lung infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Urinary tract infection	Infections and infestations	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected25 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events3 affected25 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected25 at risk
Rash acneiform	Skin and subcutaneous tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Urticaria	Skin and subcutaneous tissue disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Atrial fibrillation	Cardiac disorders	CTCAE (4.03)	Non-systematic Assessment	EG0002 events2 affected5 at risk EG0011 events1 affected25 at risk
Chest pain - cardiac	Cardiac disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Bruising	Injury, poisoning and procedural complications	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected25 at risk
Arterial injury	Injury, poisoning and procedural complications	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Insomnia	Psychiatric disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0012 events2 affected25 at risk
Delirium	Psychiatric disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Chronic kidney disease	Renal and urinary disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Hematuria	Renal and urinary disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Urinary urgency	Renal and urinary disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Thromboembolic event	Vascular disorders	CTCAE (4.03)	Non-systematic Assessment	EG0001 events1 affected5 at risk EG0013 events2 affected25 at risk
Blurred vision	Eye disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0013 events2 affected25 at risk
Cataract	Eye disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Watering eyes	Eye disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Vertigo	Ear and labyrinth disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk
Prostatic obstruction	Reproductive system and breast disorders	CTCAE (4.03)	Non-systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected25 at risk

ID	Term
D000236	Adenoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D018301	Neoplasms, Mesothelial
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D010997	Pleural Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring