Cetuximab and Bevacizumab With or Without Gemcitabine to... | NCT00326911

Label	Type	Description	Intervention Names
cetuximab + bevacizumab + gemcitabine	Experimental	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. All medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.	Biological: cetuximab Biological: bevacizumab Drug: gemcitabine
cetuximab + bevacizumab	Active Comparator	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.	Biological: cetuximab Biological: bevacizumab

Name	Type	Description	Arm Group Labels	Other Names
cetuximab	Biological	I.V. infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1	cetuximab + bevacizumab cetuximab + bevacizumab + gemcitabine

Measure	Description	Time Frame
Progression-free Survival (PFS)	Progression-free survival is the time from randomization until the date of progressive disease (PD) or death from any cause whichever is first reported. Patients who die without a reported prior progression were considered to have progresssed on the day of their death. Patients who did not progress were censored at the day of their last tumor assessment.	Time from randomization to disease progression or death from any cause (Range: 0 -10 months)

Measure	Description	Time Frame
Overall Survival (OS)	This measure is defined as the time from randomization to the date of death due to any cause. Survival of living patients or those who lost to follow-up were censored on the last date the patients were known to be alive.	Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The patient has provided signed written informed consent.
The patient is ≥18 years of age.
The patient has histologically or cytologically-confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery or has documented or suspected extrapancreatic metastases.
The patient has either (a) measurable disease as defined by Response Evaluation Criteria in Solid Tumors Version 1.0 (RECIST) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal [ULN]).
The patient's Eastern Cooperative Oncology Group (ECOG) performance status is ≤2.
The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥1500/mm3 and a platelet count ≥100,000/mm3 obtained within 2 weeks prior to the first dose of study medication.
The patient has adequate hepatic function as defined by a total bilirubin ≤2.0 mg/dL and transaminases ≤5.0 x ULN obtained within 2 weeks prior to the first dose of study medication.
The patient has adequate renal function as defined by serum creatinine ≤2.0 x ULN and urine dipstick for proteinuria ≤1+ obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥2+, then a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study. Urinalysis is also acceptable.
If the patient is on full-dose anticoagulation therapy (eg, warfarin or low molecular weight [LMW] heparin), the following criteria must be met:
- The patient has an in-range International Normalized Ratio ([INR]usually between 2 and 3) on a stable dose of oral anticoagulant or be on a stable dose of LMW heparin
- The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
If the patient is not on full-dose anticoagulation therapy, the following criteria must be met:
- The patient has adequate coagulation function as defined by INR ≤1.5
- The patient has a partial thromboplastin (PTT) ≤ULN obtained within 2 weeks prior to the first dose of study medication
If a woman, the patient agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
The patient is accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria:

Endocrine tumors or lymphoma of the pancreas
Known brain metastases
Prior therapy with an epidermal growth factor receptor (EGFR) inhibitor or vascular endothelial growth factor (VEGF) inhibitor
Prior chemotherapy, hormonal therapy, or radiation therapy for advanced pancreatic cancer, patients who received chemotherapy and/or radiation therapy in the adjuvant setting will be eligible as long as the adjuvant therapy was completed >6 months prior
Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix
Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
History of arterial thrombotic events within 9 months
History of uncontrolled hypertension (>150/100 mmHg) not on a stable regimen of anti-hypertensive therapy
History of significant bleeding events or upper or lower gastrointestinal bleeding within 9 months
History of gastrointestinal perforation within 12 months
Serious non-healing wound ulcer, bone fracture, or major surgical procedure with 28 days
If a woman, is pregnant or lactating
An employee of the investigator or study center as well as family members of the employees

Name	Affiliation	Role
E-mail: ClinicalTrials@ ImClone.com	Eli Lilly and Company	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
ImClone Investigational Site		Jonesboro	Arkansas	72401	United States
ImClone Investigational Site

PubMed Identifier	Type	Citation	Retractions
21629990	Derived	Ko AH, Youssoufian H, Gurtler J, Dicke K, Kayaleh O, Lenz HJ, Keaton M, Katz T, Ballal S, Rowinsky EK. A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. Invest New Drugs. 2012 Aug;30(4):1597-606. doi: 10.1007/s10637-011-9691-8. Epub 2011 Jun 1.

ID	Title	Description
FG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

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)

Progression-free survival is the time from randomization until the date of progressive disease (PD) or death from any cause whichever is first reported. Patients who die without a reported prior progression were considered to have progresssed on the day of their death. Patients who did not progress were censored at the day of their last tumor assessment.

The PFS was based on the modified Intent-to-Treat (mITT) population, which included any patient who enrolled, was randomized, and received any quantity of study drug.

Posted

Oct 2009

Median

95% Confidence Interval

months

Time from randomization to disease progression or death from any cause (Range: 0 -10 months)

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Units	Counts
Participants	OG00029 OG00129

Title

Denominators

Categories

Title	Measurements
	OG0003.55(2.00 to 5.59) OG0011.91(1.81 to 2.76)

Secondary

Overall Survival (OS)

This measure is defined as the time from randomization to the date of death due to any cause. Survival of living patients or those who lost to follow-up were censored on the last date the patients were known to be alive.

The overall survival was based on the mITT population.

Posted

Oct 2009

Median

95% Confidence Interval

Months

Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)

The best overall response is the number of patients with a best overall response of CR or PR, as classifed by the investigator according to the RECIST guidelines. A CR is the disappearance of all target lesions and a PR is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.

The best overall response was based on the mITT population for those patients who either had a CR or PR.

Posted

Oct 2009

Number

Participants

Tumor evaluations were performed every 8 weeks while on cetuximab therapy until PD or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab

Secondary

Percentage of Patients With Carbohydrate Antigen 19-9 (CA19-9) Response at End of Cycle 2 in Patients With Elevated Baseline Values (Equal or Greater Than 2 x Upper Limit of Normal).

CA19-9 is a tumor marker for pancreatic cancer and the level usually increases as the disease is progressing. The CA19-9 response was the percentage of patients whose CA19-9 level was declining, stable or increasing < 10% compared with baseline, divided by the total patients with elevated baseline CA19-9 in that arm.

The CA19-9 response rate was calculated for at least the 15 patients in each arm of the study at the end of the first two cycles of therapy (8 weeks) in the mITT population who had elevated CA19-9 levels at baseline.

Posted

Oct 2009

Number

Percentage of participants

First day of treatment to the end of Cycle 2, Week 1

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab

Secondary

Time to Progression (TTP)

Time to progression was defined as the time from randomization until the date of objectively confirmed tumor progression was first reported. The censoring rule was consistent with PFS except death. Patients who died from any cause were censored at the time of death or at last tumor assessment date if the death date was missing. For patients lost to follow-up, they were censored at the last tumor assessment date.

The TTP was based on the mITT population. For patients lost to follow-up, they were censored at the next scheduled visit.

Posted

Oct 2009

Median

95% Confidence Interval

months

Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Reported AEs per patient were coded according to the corresponding preferred term and system organ class in the Medical Dictionary for regulatory Activities dictionary. The National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0 was used to grade all AEs. The collection of AEs began at the time the patient received the first cetuximab dose and continued during the study until 30 days after the last dose of cetuximab. All patients who were enrolled and treated with cetuximab were assessed for safety (mITT population, as treated).

All patients who received any quantity of study therapy were included in the safety evaluation (safety population, as treated).

Posted

Oct 2009

Number

Participants

An AE was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001

Secondary

Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall QoL question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Mental Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Physical Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Emotional Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT Population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Social Activity question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Overall Spiritual Well Being question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Frequency of Pain question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Severity of Pain question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A positive score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Fatigue question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A positive score indicates improvement from baseline.

mITT Population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Level of Support, Friends and Family question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT Population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Financial Concerns Question question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. The primary analysis of pancreatic cancer symptoms was conducted using the LASA QoL questionnaire and was considered exploratory. The Legal Concerns question change from baseline to Cycle 2 Week 4 is reported. The best overall score is 10 and the worst is 0. A negative score indicates worsening from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Worst Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Least Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Average Pain (change from baseline) to Cycle 2 Week 4 is reported. The worst pain was 10 and no pain is 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Pain Right Now question (change from baseline) to Cycle 2 Week 4 is reported. The worst pain is 10 and no pain is 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Secondary

Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4

Accrual on the trial was stopped earlier than planned due to insufficient efficacy on both arms. Analysis of pain using the BPI was considered exploratory. The Interference question (change from baseline) to Cycle 2 Week 4 is reported. Complete interference is scored as 10 and no interference is scored as 0. A negative score indicates improvement from baseline.

mITT population

Posted

Oct 2009

Mean

Standard Deviation

Scores on a scale

Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

ID	Title	Description
OG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
OG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 8.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 8.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA 8.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 8.0	Systematic Assessment	EG0005 events4 affected29 at risk EG0011 events1 affected29 at risk
Nausea	Gastrointestinal disorders	MedDRA 8.0	Systematic Assessment	EG0002 events2 affected29 at risk EG0013 events3 affected29 at risk
Vomiting	Gastrointestinal disorders	MedDRA 8.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0014 events4 affected29 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 8.0	Systematic Assessment	EG0002 events1 affected29 at risk EG0013 events2 affected29 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 8.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Upper abdominal pain	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Constipation	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Gastric outlet obstruction	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Disease progression	General disorders	MedDRA (10.0)	Systematic Assessment	EG0005 events5 affected29 at risk EG0019 events9 affected29 at risk
Fatigue	General disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Pyrexia	General disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0011 events1 affected29 at risk
Asthenia	General disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Death	General disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
No adverse drug effect	General disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Hyperbilirubinemia	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Urinary tract infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0011 events1 affected29 at risk
Cellulitis	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0003 events2 affected29 at risk EG0010 events0 affected29 at risk
Enterococcal sepsis	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Otitis exterma	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Pyelonephritis	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Sepsis	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Septic shock	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Feeding tube complication	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Stent occlusion	Injury, poisoning and procedural complications	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Increased alanine aminotransferase	Investigations	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Increased aspartate aminotransferase	Investigations	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events1 affected29 at risk EG0011 events1 affected29 at risk
Cerebral hemorrhage	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events1 affected29 at risk EG0010 events0 affected29 at risk
Sedation	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Acute renal failure	Renal and urinary disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Renal failure	Renal and urinary disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0006 events6 affected29 at risk EG0012 events2 affected29 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Acneiform dermatitis	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Hypotension	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Arterial occlusive disease	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected29 at risk
Hypertension	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected29 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA (10.0)	Systematic Assessment	EG00023 events9 affected29 at risk EG0011 events1 affected29 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (10.0)	Systematic Assessment	EG00021 events9 affected29 at risk EG0010 events0 affected29 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (10.0)	Systematic Assessment	EG00022 events9 affected29 at risk EG0010 events0 affected29 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (10.0)	Systematic Assessment	EG0006 events3 affected29 at risk EG0010 events0 affected29 at risk
Tachycardia	Cardiac disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0012 events2 affected29 at risk
Cardiomegaly	Cardiac disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Nausea	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG00019 events14 affected29 at risk EG00120 events14 affected29 at risk
Vomiting	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG00017 events11 affected29 at risk EG00112 events9 affected29 at risk
Constipation	Cardiac disorders	MedDRA (10.0)	Systematic Assessment	EG00012 events11 affected29 at risk EG0017 events7 affected29 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG00013 events9 affected29 at risk EG0018 events7 affected29 at risk
Diarrhea	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG00010 events9 affected29 at risk EG0014 events4 affected29 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0006 events4 affected29 at risk EG0012 events2 affected29 at risk
Abdominal distention	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0013 events3 affected29 at risk
Upper abdominal pain	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0012 events2 affected29 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0014 events4 affected29 at risk
Oral pain	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0012 events2 affected29 at risk
Flatulence	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Hemorrhoids	Gastrointestinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Fatigue	General disorders	MedDRA (10.0)	Systematic Assessment	EG00032 events20 affected29 at risk EG00113 events10 affected29 at risk
Pyrexia	General disorders	MedDRA (10.0)	Systematic Assessment	EG0009 events8 affected29 at risk EG0013 events3 affected29 at risk
Peripheral edema	General disorders	MedDRA (10.0)	Systematic Assessment	EG00011 events7 affected29 at risk EG0015 events3 affected29 at risk
Chills	General disorders	MedDRA (10.0)	Systematic Assessment	EG0005 events4 affected29 at risk EG0013 events3 affected29 at risk
Infusion related reaction	General disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events3 affected29 at risk EG0012 events2 affected29 at risk
Pain	General disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0013 events3 affected29 at risk
Asthenia	General disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Malaise	General disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Jaundice	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0012 events2 affected29 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Hyperbilirubinemia	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Cholestatic jaundice	Hepatobiliary disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Urinary tract infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0012 events2 affected29 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG00019 events13 affected29 at risk EG00112 events9 affected29 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0018 events6 affected29 at risk
Hypomagnesemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG00012 events7 affected29 at risk EG0013 events3 affected29 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG00011 events5 affected29 at risk EG0013 events3 affected29 at risk
Hyperglycemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events2 affected29 at risk EG0012 events2 affected29 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0010 events0 affected29 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Hypermagnesemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Hypocalcemia	Metabolism and nutrition disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Extremity pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0011 events1 affected29 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0012 events2 affected29 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0011 events1 affected29 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events3 affected29 at risk EG0010 events0 affected29 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Headache	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG00014 events6 affected29 at risk EG0015 events5 affected29 at risk
Dizziness	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG0005 events5 affected29 at risk EG0011 events1 affected29 at risk
Dysgeusia	Nervous system disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0012 events2 affected29 at risk
Depression	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment	EG0006 events5 affected29 at risk EG0014 events4 affected29 at risk
Anxiety	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0014 events4 affected29 at risk
Insomnia	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0012 events2 affected29 at risk
Confusional state	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events1 affected29 at risk EG0012 events2 affected29 at risk
Mental Disorder	Psychiatric disorders	MedDRA (10.0)	Systematic Assessment	EG0000 events0 affected29 at risk EG0012 events2 affected29 at risk
Proteinuria	Renal and urinary disorders	MedDRA (10.0)	Systematic Assessment	EG0007 events6 affected29 at risk EG0012 events2 affected29 at risk
Acute renal failure	Renal and urinary disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG00010 events8 affected29 at risk EG0014 events4 affected29 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0013 events3 affected29 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0011 events1 affected29 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0003 events3 affected29 at risk EG0010 events0 affected29 at risk
Exertional dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0011 events1 affected29 at risk
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0001 events1 affected29 at risk EG0012 events2 affected29 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Acneiform dermatitis	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG00048 events22 affected29 at risk EG00127 events21 affected29 at risk
Pruritus	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Systematic Assessment	EG0005 events5 affected29 at risk EG0012 events2 affected29 at risk
Skin disorder	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events1 affected29 at risk EG0015 events5 affected29 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0011 events1 affected29 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0014 events3 affected29 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0004 events4 affected29 at risk EG0010 events0 affected29 at risk
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0010 events0 affected29 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0005 events4 affected29 at risk EG0011 events1 affected29 at risk
Hypertension	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0013 events2 affected29 at risk
Hypotension	Vascular disorders	MedDRA (10.0)	Systematic Assessment	EG0002 events2 affected29 at risk EG0011 events1 affected29 at risk

ID	Term
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description
BG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
BG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab, bevacizumab, and gemcitabine. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.			21	29	29	29
EG001	Cetuximab + Bevacizumab	Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.			16	29	29	29

ID	Term
D000068818	Cetuximab
D000068258	Bevacizumab
D000093542	Gemcitabine