Selinexor Treatment of Advanced Relapsed/Refractory Squam... | NCT02213133

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1: Head and Neck-SCC	Experimental	Participants with advanced squamous cell carcinoma (SCC) of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 milligram (mg) selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets less than [<] 100*10^9 per litre [/L]), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Drug: Selinexor (KPT-330)
Cohort 2: Lungs-SCC	Experimental	Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	Drug: Selinexor (KPT-330)
Cohort 3: Esophagus-SCC	Experimental	Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Selinexor (KPT-330)	Drug	Oral tablet or suspension at 60, 80, 100 or 120 mg per patient-specific body surface area category. Dosing will occur twice weekly in 28-days cycle.	Cohort 1: Head and Neck-SCC

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	DCR was defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participant response was evaluated by physical examinations and computed tomography (CT)/Magnetic Resonance Imaging (MRI) (or optional positron emission tomography [PET]/CT) and assessed by RECIST 1.1 criteria.	up to 14.6 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was defined as any unfavorable sign and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of the study drug, whether or not related to study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose (including after informed consent was signed and prior to dosing) that resulted in death, was life-threatening (participant was at immediate risk of death from event), required in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect, and important medical events. A TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after first dose of treatment through 30 days following last dose of study treatment, or any event considered drug-related by investigator through end of study.

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado Cancer Center		Aurora	Colorado	80045	United States
Lee Moffitt Cancer Center and Research Institute

ID	Title	Description
FG000	Cohort 1: Head and Neck-SCC	Participants with advanced squamous cell carcinoma (SCC) of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 milligrams (mg) selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets less than [<] 100*10^9 per litre [/L]), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.

Arm/Group Information

ID	Title	Description
BG000	Cohort 1: Head and Neck-SCC	Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
BG001	Cohort 2: Lungs-SCC	Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
BG002	Cohort 3: Esophagus-SCC	Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00033 BG0014 BG0021 BG00338

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 With Disease Control Rate (DCR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

DCR was defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Participant response was evaluated by physical examinations and computed tomography (CT)/Magnetic Resonance Imaging (MRI) (or optional positron emission tomography [PET]/CT) and assessed by RECIST 1.1 criteria.

Analysis performed on mITT population that included all participants who received at least 1 dose of study drug, and had at least 1 post baseline efficacy assessment. Participants who discontinued prior to first post baseline efficacy assessment were included if discontinuation was due to disease progression, study drug related toxicity, or death.

Posted

Number

95% Confidence Interval

percentage of participants

up to 14.6 months

ID	Title	Description
OG000	Cohort 1: Head and Neck-SCC	Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
OG001	Cohort 2: Lungs-SCC	Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.
OG002	Cohort 3: Esophagus-SCC	Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.

Units	Counts
Participants	OG00033 OG0014 OG0021

Title

Denominators

Categories

Title	Measurements
	OG00021.2(10.7 to 37.8) OG0010.0(0.0 to 49.0) OG0020.0(0.0 to 79.3)

Secondary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

An adverse event (AE) was defined as any unfavorable sign and unintended sign (including abnormal laboratory finding), symptom, or disease temporarily associated with the use of the study drug, whether or not related to study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose (including after informed consent was signed and prior to dosing) that resulted in death, was life-threatening (participant was at immediate risk of death from event), required in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect, and important medical events. A TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after first dose of treatment through 30 days following last dose of study treatment, or any event considered drug-related by investigator through end of study.

Analysis was performed on safety population that included all participants who had received any amount of study drug.

Posted

Count of Participants

Participants

From the first administration of study drug up to 30 days follow-up (up to 14.6 months)

ID	Title	Description
OG000	Cohort 1: Head and Neck-SCC	Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.

Secondary

Number of Participants With Treatment-emergent Adverse Events by Severity: Clinical Terminology Categories for Adverse Events (CTCAE) Grading Scale

AE:Any unfavorable sign and unintended sign,symptom, or disease temporarily associated with use of study drug, whether or not related to it. SAE:Any untoward medical occurrence that occurs at any dose (after informed consent was signed, prior dosing) that resulted in death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, and important medical events. TEAE:Any AE with onset or worsening of existing condition on or after first dose through 30 days following last dose of study drug, or any event considered drug-related by investigator through end of study. Severity(Grades 1 to 5) of each AE was categorized as either mild=1(transient,does not interfere with daily activities), moderate=2(low level of inconvenience or concern,interfere with daily activities), severe=3(interrupt usual daily activities), life threatening=4 or fatal=5, higher grade reported worst outcome.

Analysis was performed on safety population that included all participants who had received any amount of study drug.

Posted

Count of Participants

Participants

From the first administration of study drug up to 30 days follow-up (up to 14.6 months)

ID	Title	Description
OG000	Cohort 1: Head and Neck-SCC	Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.

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	Cohort 1: Head and Neck-SCC	Participants with advanced SCC of head and neck, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	16	37	18	37	35	37
EG001	Cohort 2: Lungs-SCC	Participants with advanced SCC of lungs, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	2	5	2	5	5	5
EG002	Esophagus-SCC	Participants with advanced SCC of esophagus, who had relapsed or had metastasis following chemotherapy, received a fixed dose of 60 mg selinexor oral tablets twice weekly on Days 1 and 3 of a 28-day cycle (8 doses in 4 weeks) until disease progression or development of unacceptable toxicities. After completion of Cycle 2, for participants with absence of any grade 2 toxicity and thrombocytopenia (platelets <100*10^9/L), dose may be increased to 80 mg selinexor oral tablets twice weekly as assessed by investigator in a 28-day cycle until disease progression or development of unacceptable toxicities.	1	3	3	3	3	3

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0005 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Lung Infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Tracheitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0022 affected3 at risk
Arthritis Bacterial	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Skin Infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Streptococcal Bacteraemia	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Laryngeal Obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Obstructive Airways Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Delirium	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Anxiety	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Mouth Haemorrhage	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Tracheal Obstruction	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Death	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Platelet Count Decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hypotension	Vascular disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG00025 affected37 at risk EG0014 affected5 at risk EG0020 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG00013 affected37 at risk EG0012 affected5 at risk EG0020 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG00010 affected37 at risk EG0011 affected5 at risk EG0021 affected3 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0005 affected37 at risk EG0012 affected5 at risk EG0021 affected3 at risk
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Fatigue	General disorders	MedDRA 16.0	Systematic Assessment	EG00021 affected37 at risk EG0014 affected5 at risk EG0021 affected3 at risk
Pyrexia	General disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0022 affected3 at risk
Asthenia	General disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Face Oedema	General disorders	MedDRA 16.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Chills	General disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Pain	General disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG00015 affected37 at risk EG0011 affected5 at risk EG0021 affected3 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG00012 affected37 at risk EG0012 affected5 at risk EG0021 affected3 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0008 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0006 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0004 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0007 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0005 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Productive Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Weight Decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0006 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Platelet Count Decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0011 affected5 at risk EG0021 affected3 at risk
Blood Creatinine Increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Lymphocyte Count Decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Dizziness	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0005 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Dysgeusia	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Headache	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hemiparesis	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Syncope	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Insomnia	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0011 affected5 at risk EG0021 affected3 at risk
Agitation	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Anxiety	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Confusional State	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hallucination	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment	EG0009 affected37 at risk EG0011 affected5 at risk EG0022 affected3 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected5 at risk EG0021 affected3 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Pain In Jaw	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Lung Infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Vision Blurred	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0006 affected37 at risk EG0012 affected5 at risk EG0020 affected3 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected37 at risk EG0010 affected5 at risk EG0020 affected3 at risk
Hypotension	Vascular disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Ear Pain	Ear and labyrinth disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0011 affected5 at risk EG0020 affected3 at risk
Pericardial Effusion	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk
Sinus Tachycardia	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected37 at risk EG0010 affected5 at risk EG0021 affected3 at risk

ID	Term
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma

ID	Term
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D018307	Neoplasms, Squamous Cell