A Study for Patients With Recurrent or Metastatic Squamou... | NCT01057589

ID	Type	Description	Link
H3E-MC-S123	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Pemetrexed + Cisplatin + Cetuximab	Experimental	Participants will receive pemetrexed,cisplatin and cetuximab for up to 6 cycles (21 days per cycle) followed by optional maintenance of pemetrexed and cetuximab until disease progression. Optional maintenance therapy is permitted after at least 4 cycles of triplet combination therapy have been given. Cetuximab will be administered as an initial dose of 400 milligram per meter squared (mg/m^2) intravenous (IV) infusion and as a 250 mg/m^2 IV weekly dose thereafter. As Standard of care dietary supplements included: 350 to 1000 micrograms (µg) oral Folic Acid 5 times a day for the 7 days preceding the first dose of first dose of pemetrexed and continuing throughout treatment and for 21 days after the last dose of pemetrexed and 1000 µg vitamin B12 intramuscular injection (IM) during the week preceding the first dose of pemetrexed and every 9 weeks thereafter.	Drug: Pemetrexed Drug: Cetuximab Drug: Cisplatin Dietary Supplement: Folic Acid Dietary Supplement: Vitamin B12

Name	Type	Description	Arm Group Labels	Other Names
Pemetrexed	Drug	Triplet Combination Therapy: 500 mg/m^2 administered intravenously on Day 1 of 21 day cycle for up to 6 cycles Maintenance Therapy: 500mg/m^2 administered intravenously on Day 1 of 21 day cycle until disease progression or unacceptable toxicity

Measure	Description	Time Frame
Progression Free Survival (PFS)	PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Baseline to date of PD or death up to 18.7 months

Measure	Description	Time Frame
Overall Survival (OS)	OS defined as the time from the date of first dose of study drug to the date to death from any cause.	Baseline to date of death up to 18.7 months
Percent of Participants With a Partial Response (PR) or a Complete Response (CR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed diagnosis of squamous cell carcinoma of head and neck (SCCHN)
Recurrent or metastatic SCCHN, not amenable to local therapy
At least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy)
No more than 1 prior systemic therapy, given as part of multimodal treatment for locally advanced disease;
No prior systemic therapy for metastatic disease
Radiation therapy must be completed at least 4 weeks before study enrollment.
For palliative therapy, prior radiation therapy allowed to <25% of the bone marrow (Cristy and Eckerman 1987), and prior radiation to the whole pelvis is not allowed.
Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment.
An estimated life expectancy of at least 12 weeks.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Oken et al. 1982).
Biological tissue available for biomarker analysis on tumor tissue.
Disease status may be measurable or nonmeasurable as defined by Response Evaluation Criteria in Solid Tumors
Patient compliance and geographic proximity that allow for adequate follow-up.
Adequate organ function
Willingness to comply with Contraceptive Regimen
For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen [for example, intrauterine device (IUD), birth control pills, or barrier device] during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period.

Exclusion Criteria:

Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer.
Previously received treatment with monoclonal antibody therapy, or other signal transduction inhibitors of Epidermal Growth Factor Receptor therapy.
Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer.
Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
Have serious cardiac disease, such as symptomatic , unstable angina, or the history of myocardial infarction in the previous 12 months.
Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
Have had another primary malignancy other than Head and Neck cancer, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Patients with a history of in situ carcinoma of the cervix, nonmelanoma skin cancer, or low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously.
Presence of clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry.
Have peripheral neuropathy
Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients.
Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids.
Recent (within 30 days before enrollment) or concurrent yellow fever vaccination.
Pregnant or breast-feeding

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5PM Eastern time (UTC/GMT - 5 hours, EST	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Edegem		2650

PubMed Identifier	Type	Citation
	Background	Cristy M, Eckerman KF. 1987. Specific absorbed fractions of energy at various ages from internal sources: I. methods. Prepared by the Oak Ridge National Laboratory, Oak Ridge, Tenn.
7165009	Background	Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
23726971

ID	Title	Description
FG000	Pemetrexed + Cisplatin + Cetuximab	Pemetrexed 500 milligram per meter squared (mg/m^2) administered by intravenous (IV) infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

ID	Title	Description
BG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Units	Counts
Participants	BG00066

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

Progression Free Survival (PFS)

PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines defined as the time from the date of first dose of study drug to first documented objective progressive disease (PD) or death from any cause. PD is defined as at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Protocol Qualified (PQ) Population: all randomized and treated participants

Posted

Median

95% Confidence Interval

months

Baseline to date of PD or death up to 18.7 months

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Units	Counts
Participants	OG00066

Title

Denominators

Categories

Title	Measurements
	OG0004.4(3.6 to 5.4)

Secondary

Overall Survival (OS)

OS defined as the time from the date of first dose of study drug to the date to death from any cause.

PQ Population: all randomized and treated participants

Posted

Median

95% Confidence Interval

months

Baseline to date of death up to 18.7 months

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Units	Counts
Participants	OG000

Secondary

Percent of Participants With a Partial Response (PR) or a Complete Response (CR)

CR and PR based on RECIST Guidelines: CR is defined as the disappearance of all tumor lesions; PR is defined as at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LDs or the complete disappearance of target lesions, with persistence (but not worsening) of one or more nontarget lesions and the appearance of no new lesions. PD is defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

PQ Population: all randomized and treated participants with evaluable data; 6 participant's results were unknown.

Posted

Number

95% Confidence Interval

percentage of participants

Date of first response to PD (up to 18.7 months)

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Secondary

Change From Baseline in Participant Reported European-Quality of Life 5 Dimension Instrument (EQ-5D) Visual Analog Scale (VAS) at End of Triplet Combination Therapy and End of Maintenance Therapy

Vertical VAS - a 20 millimeter (mm), fractionated scale in the form of a thermometer with endpoints of 0 (worst imaginable health state) and 100 (best imaginable health state). Participants used the EQ-5D VAS scale to rate their overall health on the day the questionnaire was administered. Possible change values range from -100 (best imaginable health at baseline changed to worst possible health at visit) to 100 (worst possible health at baseline changed to best possible health at visit).

PQ Population: all randomized and treated participants with evaluable data for each category

Posted

Mean

Standard Deviation

units on a scale

Baseline, End of Triplet Combination Therapy (up to Cycle 6 [4.2 months]), End of Maintenance Therapy (up to 18.7 months)

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Secondary

Change From Baseline in Participant Reported EQ-5D Utility Score at End of Triplet Combination Therapy and End of Maintenance Therapy

EQ-5D Index is derived by converting the Descriptive System (participant is required to rate health by checking 1 [no limitation], 2 [some limitation] or 3 [severe or complete limitation] in 5 dimensions [mobility, self-care, usual activities, pain/comfort and anxiety/depression]) to a single summary index. A utility value assigned to each individual's health state based on the absence or presence of moderate or severe problems in the 5 dimensions. A regression equation defines a utility value for these health states. The possible values for health utility ranged from -0.59 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 0 represents death and 1 represents the best possible health state. Possible change values range from -1.59 (no problems at baseline to severe problems at visit) to 1.59 (severe problems at baseline to no problems at visit).

PQ Population: all randomized and treated participants with EQ-5D data at respective timepoint.

Posted

Mean

Standard Deviation

units on a scale

Baseline, End of Triplet Combination Therapy (up to 6 cycles [4.2 months]) , End of Maintenance Therapy (up to 18.7 months)

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Secondary

Change From Baseline in Performance Status Scale for Head and Neck Cancer Patients (PSS-HNC)

PSS-HNC is a clinician-rated instrument designed to measure speaking and eating disabilities of participants with head and neck cancer and consists of 3 subscales: Normalcy of Diet (NOD) subscale measures the ability of the participants to eat a normal diet, scale ranged from 0 (non-oral feeding) to 100 (unrestricted diet); Understandability of Speech (UOS)subscale measured the degree a clinician was able to understand the participant's speech, subscale ranged from 0 (never understandable) to 100 (always understandable); Eating in Public (EIP) subscale, rating based on clinician question to the participant to report who he/she eats with and in what setting, subscale ranged from 0 (always eats alone) to 100 (no restriction of place, food, or companion). Change from baseline: negative value represents a decrease in function and a positive value represents an increase in function.

PQ Population: all randomized and treated participants with evaluable data at respective timepoint.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Triplet Combination Therapy Cycles 2, 4, 6 (cycle = 21 days) and optional Maintenance Therapy Cycles 1, 3, 5 and 7 (cycle = 21 days)

ID	Title	Description
OG000	Pemetrexed Cisplatin Cetuximab	Pemetrexed 500 mg/m^2 administered by IV infusion followed by cisplatin 75 mg/m^2 administered by IV infusion both given on Day 1 of each 21 day cycle. Cetuximab 400 mg/m^2 administered by IV infusion initially as a loading dose in Week 1, subsequent weeks cetuximab 250 mg/m^2 administered by IV infusion once per week for a maximum of six 21 day cycles. At the discretion of the investigator participants who completed at least 4 cycles of triplet combination therapy could continue to receive pemetrexed plus cetuximab in the maintenance setting or as a monotherapy of pemetrexed or cetuximab alone in the absence of PD, unacceptable toxicity or any other withdrawal criterion up to 19 months. Participants also received Folic Acid and Vitamin B12 as standard of care dietary supplements.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0007 events4 affected66 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected66 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0006 events3 affected66 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0005 events3 affected66 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Fanconi syndrome	Congenital, familial and genetic disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0005 events4 affected66 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Subileus	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events2 affected66 at risk
Asthenia	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Death	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
General physical health deterioration	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Implant site haemorrhage	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Malaise	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Medical device complication	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Medical device pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Mucosal inflammation	General disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Performance status decreased	General disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG0004 events3 affected66 at risk
Anaphylactic shock	Immune system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Bronchitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Catheter site infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Endocarditis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Pneumonia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0007 events7 affected66 at risk
Postoperative wound infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0004 events3 affected66 at risk
Sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Septic embolus	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Septic shock	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Blood creatinine increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Weight decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0004 events3 affected66 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Tumour embolism	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Asterixis	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Cerebral infarction	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Syncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected66 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Renal failure	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected66 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0002 events2 affected66 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0003 events3 affected66 at risk
Haemorrhage	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0001 events1 affected66 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected66 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00030 events26 affected66 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00036 events26 affected66 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00035 events26 affected66 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 12.0	Systematic Assessment	EG00019 events16 affected66 at risk
Conjunctivitis	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0007 events6 affected66 at risk
Lacrimation increased	Eye disorders	MedDRA 12.0	Systematic Assessment	EG0005 events4 affected66 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events4 affected66 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0007 events7 affected66 at risk
Constipation	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00029 events25 affected66 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00028 events20 affected66 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00011 events10 affected66 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00013 events12 affected66 at risk
Nausea	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00033 events27 affected66 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00024 events20 affected66 at risk
Vomiting	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG00026 events22 affected66 at risk
Asthenia	General disorders	MedDRA 12.0	Systematic Assessment	EG00025 events14 affected66 at risk
Chills	General disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Fatigue	General disorders	MedDRA 12.0	Systematic Assessment	EG00045 events40 affected66 at risk
Mucosal inflammation	General disorders	MedDRA 12.0	Systematic Assessment	EG00035 events22 affected66 at risk
Oedema peripheral	General disorders	MedDRA 12.0	Systematic Assessment	EG0009 events7 affected66 at risk
Pain	General disorders	MedDRA 12.0	Systematic Assessment	EG0005 events4 affected66 at risk
Pyrexia	General disorders	MedDRA 12.0	Systematic Assessment	EG00012 events12 affected66 at risk
Folliculitis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected66 at risk
Oral candidiasis	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0005 events4 affected66 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Weight decreased	Investigations	MedDRA 12.0	Systematic Assessment	EG00010 events10 affected66 at risk
Weight increased	Investigations	MedDRA 12.0	Systematic Assessment	EG0006 events4 affected66 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00031 events29 affected66 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Fluid retention	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00010 events6 affected66 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected66 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00026 events20 affected66 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG00024 events21 affected66 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 12.0	Systematic Assessment	EG0008 events6 affected66 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected66 at risk
Dizziness	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG00018 events15 affected66 at risk
Dysgeusia	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0008 events7 affected66 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected66 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Syncope	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected66 at risk
Insomnia	Psychiatric disorders	MedDRA 12.0	Systematic Assessment	EG0007 events7 affected66 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events6 affected66 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0005 events4 affected66 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG00012 events11 affected66 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0009 events9 affected66 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 12.0	Systematic Assessment	EG0006 events5 affected66 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00011 events11 affected66 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00012 events11 affected66 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0006 events5 affected66 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00017 events14 affected66 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00010 events10 affected66 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected66 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0005 events5 affected66 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00037 events31 affected66 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG00012 events11 affected66 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0004 events4 affected66 at risk
Hypotension	Vascular disorders	MedDRA 12.0	Systematic Assessment	EG0008 events7 affected66 at risk

ID	Term
D006258	Head and Neck Neoplasms
D007818	Laryngeal Diseases
D013959	Thyroid Diseases

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D012140	Respiratory Tract Diseases
D010038	Otorhinolaryngologic Diseases
D004700	Endocrine System Diseases

ID	Term
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D012712	Serum Globulins
D005916	Globulins
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D011622	Pterins
D011621	Pteridines
D045728	Corrinoids
D045725	Tetrapyrroles
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006576	Heterocyclic Compounds, 4 or More Rings
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds

ID	Term
D000068437	Pemetrexed
D000068818	Cetuximab
D002945	Cisplatin
D005492	Folic Acid
D014805	Vitamin B 12