Cetuximab and Bevacizumab With or Without Gemcitabine to Treat Metastatic Pancreatic Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00326911
• Collaborator: (none)
• Enrollment: 61
• Locations: 16
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Eligible patients with metastatic pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Cancer	Biological: cetuximab; Biological: bevacizumab; Drug: gemcitabine; Biological: cetuximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Open-Label Study of Cetuximab and Bevacizumab Alone or in Combination With Fixed-Dose Rate Gemcitabine as First-Line Therapy of Patients With Metastatic Adenocarcinoma of the Pancreas
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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. 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; I.V. infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1; Other Names: Erbitux® ; Biological: bevacizumab; 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.; Other Names: Avastin® ; Drug: gemcitabine; 1000 mg/m2 administered intravenously at 10 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks.; Other Names: Gemzar® ; Biological: cetuximab; I.V.infusions of 250 mg/m2 (over 60 minutes) weekly; Other Names: Erbitux®
Active Comparator: 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.	Biological: cetuximab; I.V. infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1; Other Names: Erbitux® ; Biological: bevacizumab; 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.; Other Names: Avastin® ; Biological: cetuximab; I.V.infusions of 250 mg/m2 (over 60 minutes) weekly; Other Names: Erbitux®

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Time from randomization to disease progression or death from any cause (Range: 0 -10 months)]

   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.

Secondary Outcome Measures

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

   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.

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

   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.

3. 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). [First day of treatment to the end of Cycle 2, Week 1]

   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.

4. Time to Progression (TTP) [Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)]

   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.

5. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [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.]

   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).

6. Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

   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.

7. Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

   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.

8. Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

   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.

9. Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

   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.

10. Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

11. Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug]

    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.

12. Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

13. Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug]

    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.

14. Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

15. Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

16. Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

17. Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

18. Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

19. Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

20. Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

21. Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

22. Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4 [Screening, and then every 8 weeks while receiving study drug to 30-day follow-up]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Jonesboro	Arkansas	United States	72401
2	ImClone Investigational Site	San Francisco	California	United States	94115
3	ImClone Investigational Site	Stamford	Connecticut	United States	06902
4	ImClone Investigational Site	Miami	Florida	United States	33176
5	ImClone Investigational Site	Orlando	Florida	United States	32804
6	ImClone Investigational Site	Orlando	Florida	United States	32806
7	ImClone Investigational Site	Atlanta	Georgia	United States	30309
8	ImClone Investigational Site	Augusta	Georgia	United States	30901
9	ImClone Investigational Site	Marietta	Georgia	United States	30060
10	ImClone Investigational Site	Metairie	Louisiana	United States	70006
11	ImClone Investigational Site	Billings	Montana	United States	59101
12	ImClone Investigational Site	Concord	North Carolina	United States	28025
13	ImClone Investigational Site	Philadelphia	Pennsylvania	United States	19106
14	ImClone Investigational Site	Charleston	South Carolina	United States	29406
15	ImClone Investigational Site	Arlington	Texas	United States	76012
16	ImClone Investigational Site	Dallas	Texas	United States	75230

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Chair: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00326911
• Other Study ID Numbers: CP02-0555
• First Posted: May 17, 2006
• Last Update Posted: May 25, 2011
• Last Verified: May 1, 2011

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Bevacizumab; Cetuximab

Study Results

Participant Flow

Recruitment Details	Patients were recruited from a population of pancreatic cancer patients treated at investigational centers.
Pre-assignment Detail	Prior chemotherapy, hormonal therapy, radiation therapy in the adjuvant setting were allowed, provided that the last date of therapy was at least 6 months prior to randomization.

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	30	31
COMPLETED	29	29
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	30	31	61
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 60%	18 58.1%	36 59%
>=65 years	12 40%	13 41.9%	25 41%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.7 (11.6)	62.2 (11.4)	62.4 (11.4)
Sex: Female, Male (Count of Participants)
Female	11 36.7%	15 48.4%	26 42.6%
Male	19 63.3%	16 51.6%	35 57.4%
Region of Enrollment (participants) [Number]
United States	30 100%	31 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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 Frame	Time from randomization to disease progression or death from any cause (Range: 0 -10 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	29	29
Median (95% Confidence Interval) [months]	3.55	1.91

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The overall survival was based on the mITT population.

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	29	29
Median (95% Confidence Interval) [Months]	5.41	4.17

3. Secondary Outcome

Title	The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	29	29
Number [Participants]	4 13.3%	0 0%

4. Secondary Outcome

Title	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).
Description	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.
Time Frame	First day of treatment to the end of Cycle 2, Week 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	18	19
Number [Percentage of participants]	8 26.7%	9 29%

5. Secondary Outcome

Title	Time to Progression (TTP)
Description	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.
Time Frame	Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	29	29
Median (95% Confidence Interval) [months]	4.11	2.07

6. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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).
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	29	29
Number [Participants]	29 96.7%	29 93.5%

7. Secondary Outcome

Title	Change From Baseline in Quality of Life (QoL) Assessment Using the Linear Analog Scale Assessment (LASA), Overall QoL at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.9 (2.9)	-0.9 (2.3)

8. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Overall Mental Well Being, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	11
Mean (Standard Deviation) [Scores on a scale]	0.6 (2.0)	-0.8 (1.4)

9. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Overall Physical Well Being, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.6 (3.1)	-0.6 (1.7)

10. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Overall Emotional Well Being, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	11
Mean (Standard Deviation) [Scores on a scale]	-0.2 (2.8)	-1.1 (2.1)

11. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Level of Social Activity, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-1.1 (2.9)	0.6 (2.3)

12. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Overall Spiritual Well Being, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	11
Mean (Standard Deviation) [Scores on a scale]	-0.4 (1.8)	-0.3 (1.1)

13. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Frequency of Pain, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-1.5 (2.9)	-2.3 (2.6)

14. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Severity of Pain, Average, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up while receiving study drug

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.5 (2.8)	-0.9 (2.4)

15. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Level of Fatigue, Average, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	1.5 (2.3)	0.3 (2.6)

16. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Level of Support, Friends and Family, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	0.1 (1.3)	-0.8 (1.5)

17. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Financial Concerns, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.1 (2.4)	0.9 (3.7)

18. Secondary Outcome

Title	Change From Baseline in QoL Assessment Using LASA, Legal Concerns, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	0.4 (1.7)	2.3 (3.2)

19. Secondary Outcome

Title	Change From Baseline in Assessment of Pain Using the Brief Pain Inventory (BPI) Short Form, Worst Pain, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-1.2 (2.8)	0.5 (2.5)

20. Secondary Outcome

Title	Change From Baseline in Assessment of Pain Using BPI Short Form, Least Pain, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.4 (2.0)	0.9 (2.4)

21. Secondary Outcome

Title	Change From Baseline in Assessment of Pain Using BPI Short Form, Average Pain, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.6 (1.8)	-0.2 (2.1)

22. Secondary Outcome

Title	Change From Baseline in Assessment of Pain Using BPI Short Form, Pain Right Now, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	17	12
Mean (Standard Deviation) [Scores on a scale]	-0.9 (2.6)	0.9 (2.0)

23. Secondary Outcome

Title	Change From Baseline in Assessment of Pain Using BPI Short Form, Interference, at Cycle 2 Week 4
Description	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.
Time Frame	Screening, and then every 8 weeks while receiving study drug to 30-day follow-up

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine	Cetuximab + Bevacizumab
Arm/Group Description	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.	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.
Measure Participants	16	12
Mean (Standard Deviation) [Scores on a scale]	-0.2 (2.3)	0.8 (2.9)

Adverse Events

Time Frame	Adverse events were collected beginning at the time the patient received the initial cetuximab infusion and continued throughout the study until 30 days after the last dose.
Arm/Group Title	Cetuximab + Bevacizumab + Gemcitabine		Cetuximab + Bevacizumab
Arm/Group Description	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.		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.
All Cause Mortality
	Cetuximab + Bevacizumab + Gemcitabine		Cetuximab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cetuximab + Bevacizumab + Gemcitabine		Cetuximab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/29 (72.4%)		16/29 (55.2%)
Blood and lymphatic system disorders
Thrombocytopenia	1/29 (3.4%)	1	0/29 (0%)	0
Cardiac disorders
Atrial Fibrillation	1/29 (3.4%)	1	0/29 (0%)	0
Cardio-Respiratory Arrest	1/29 (3.4%)	1	0/29 (0%)	0
Gastrointestinal disorders
Abdominal Pain	4/29 (13.8%)	5	1/29 (3.4%)	1
Nausea	2/29 (6.9%)	2	3/29 (10.3%)	3
Vomiting	1/29 (3.4%)	1	4/29 (13.8%)	4
Gastrointestinal Haemorrhage	1/29 (3.4%)	2	2/29 (6.9%)	3
Diarrhoea	0/29 (0%)	0	2/29 (6.9%)	2
Upper abdominal pain	0/29 (0%)	0	1/29 (3.4%)	1
Constipation	1/29 (3.4%)	1	0/29 (0%)	0
Gastric outlet obstruction	0/29 (0%)	0	1/29 (3.4%)	1
Intestinal obstruction	1/29 (3.4%)	1	0/29 (0%)	0
Small intestinal obstruction	0/29 (0%)	0	1/29 (3.4%)	1
General disorders
Disease progression	5/29 (17.2%)	5	9/29 (31%)	9
Fatigue	2/29 (6.9%)	2	0/29 (0%)	0
Pyrexia	1/29 (3.4%)	1	1/29 (3.4%)	1
Asthenia	1/29 (3.4%)	1	0/29 (0%)	0
Death	1/29 (3.4%)	1	0/29 (0%)	0
No adverse drug effect	0/29 (0%)	0	1/29 (3.4%)	1
Hepatobiliary disorders
Hepatic failure	1/29 (3.4%)	1	0/29 (0%)	0
Hyperbilirubinemia	0/29 (0%)	0	1/29 (3.4%)	1
Portal vein thrombosis	1/29 (3.4%)	1	0/29 (0%)	0
Infections and infestations
Urinary tract infection	2/29 (6.9%)	2	1/29 (3.4%)	1
Cellulitis	2/29 (6.9%)	3	0/29 (0%)	0
Enterococcal sepsis	1/29 (3.4%)	1	0/29 (0%)	0
Otitis exterma	1/29 (3.4%)	1	0/29 (0%)	0
Pyelonephritis	1/29 (3.4%)	1	0/29 (0%)	0
Sepsis	1/29 (3.4%)	1	0/29 (0%)	0
Septic shock	1/29 (3.4%)	1	0/29 (0%)	0
Injury, poisoning and procedural complications
Feeding tube complication	0/29 (0%)	0	1/29 (3.4%)	1
Overdose	1/29 (3.4%)	1	0/29 (0%)	0
Stent occlusion	0/29 (0%)	0	1/29 (3.4%)	1
Investigations
Increased alanine aminotransferase	0/29 (0%)	0	1/29 (3.4%)	1
Increased aspartate aminotransferase	0/29 (0%)	0	1/29 (3.4%)	1
Metabolism and nutrition disorders
Failure to thrive	2/29 (6.9%)	2	0/29 (0%)	0
Anorexia	1/29 (3.4%)	1	0/29 (0%)	0
Dehydration	1/29 (3.4%)	1	0/29 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/29 (3.4%)	1	0/29 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/29 (3.4%)	2	1/29 (3.4%)	1
Cerebral hemorrhage	1/29 (3.4%)	2	0/29 (0%)	0
Sedation	0/29 (0%)	0	1/29 (3.4%)	1
Renal and urinary disorders
Acute renal failure	0/29 (0%)	0	2/29 (6.9%)	2
Renal failure	1/29 (3.4%)	1	0/29 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	6/29 (20.7%)	6	2/29 (6.9%)	2
Dyspnea	2/29 (6.9%)	2	0/29 (0%)	0
Chronic obstructive pulmonary disease	1/29 (3.4%)	1	0/29 (0%)	0
Skin and subcutaneous tissue disorders
Acneiform dermatitis	0/29 (0%)	0	1/29 (3.4%)	1
Vascular disorders
Deep vein thrombosis	2/29 (6.9%)	2	0/29 (0%)	0
Hypotension	0/29 (0%)	0	2/29 (6.9%)	2
Arterial occlusive disease	1/29 (3.4%)	1	0/29 (0%)	0
Hypertension	0/29 (0%)	0	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Cetuximab + Bevacizumab + Gemcitabine		Cetuximab + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/29 (100%)		29/29 (100%)
Blood and lymphatic system disorders
Anemia	9/29 (31%)	23	1/29 (3.4%)	1
Neutropenia	9/29 (31%)	21	0/29 (0%)	0
Thrombocytopenia	9/29 (31%)	22	0/29 (0%)	0
Leukopenia	3/29 (10.3%)	6	0/29 (0%)	0
Cardiac disorders
Tachycardia	1/29 (3.4%)	1	2/29 (6.9%)	2
Cardiomegaly	2/29 (6.9%)	2	0/29 (0%)	0
Constipation	11/29 (37.9%)	12	7/29 (24.1%)	7
Gastrointestinal disorders
Nausea	14/29 (48.3%)	19	14/29 (48.3%)	20
Vomiting	11/29 (37.9%)	17	9/29 (31%)	12
Stomatitis	9/29 (31%)	13	7/29 (24.1%)	8
Diarrhea	9/29 (31%)	10	4/29 (13.8%)	4
Abdominal pain	4/29 (13.8%)	6	2/29 (6.9%)	2
Abdominal distention	2/29 (6.9%)	2	3/29 (10.3%)	3
Upper abdominal pain	3/29 (10.3%)	3	2/29 (6.9%)	2
Dyspepsia	1/29 (3.4%)	1	4/29 (13.8%)	4
Oral pain	2/29 (6.9%)	2	2/29 (6.9%)	2
Flatulence	2/29 (6.9%)	2	0/29 (0%)	0
Hemorrhoids	2/29 (6.9%)	2	0/29 (0%)	0
General disorders
Fatigue	20/29 (69%)	32	10/29 (34.5%)	13
Pyrexia	8/29 (27.6%)	9	3/29 (10.3%)	3
Peripheral edema	7/29 (24.1%)	11	3/29 (10.3%)	5
Chills	4/29 (13.8%)	5	3/29 (10.3%)	3
Infusion related reaction	3/29 (10.3%)	4	2/29 (6.9%)	2
Pain	2/29 (6.9%)	2	3/29 (10.3%)	3
Asthenia	2/29 (6.9%)	2	0/29 (0%)	0
Malaise	2/29 (6.9%)	2	0/29 (0%)	0
Hepatobiliary disorders
Jaundice	3/29 (10.3%)	3	2/29 (6.9%)	2
Bile duct obstruction	2/29 (6.9%)	2	0/29 (0%)	0
Hyperbilirubinemia	2/29 (6.9%)	2	0/29 (0%)	0
Cholestatic jaundice	2/29 (6.9%)	2	0/29 (0%)	0
Infections and infestations
Urinary tract infection	4/29 (13.8%)	4	2/29 (6.9%)	2
Upper respiratory tract infection	0/29 (0%)	0	2/29 (6.9%)	2
Metabolism and nutrition disorders
Anorexia	13/29 (44.8%)	19	9/29 (31%)	12
Dehydration	4/29 (13.8%)	4	6/29 (20.7%)	8
Hypomagnesemia	7/29 (24.1%)	12	3/29 (10.3%)	3
Hypokalemia	5/29 (17.2%)	11	3/29 (10.3%)	3
Hyperglycemia	2/29 (6.9%)	3	2/29 (6.9%)	2
Hyperkalemia	3/29 (10.3%)	3	0/29 (0%)	0
Decreased appetite	0/29 (0%)	0	2/29 (6.9%)	2
Hypermagnesemia	2/29 (6.9%)	2	0/29 (0%)	0
Hypocalcemia	2/29 (6.9%)	2	0/29 (0%)	0
Musculoskeletal and connective tissue disorders
Extremity pain	3/29 (10.3%)	3	1/29 (3.4%)	1
Back pain	1/29 (3.4%)	1	2/29 (6.9%)	2
Musculoskeletal chest pain	2/29 (6.9%)	2	1/29 (3.4%)	1
Myalgia	3/29 (10.3%)	4	0/29 (0%)	0
Muscular weakness	2/29 (6.9%)	2	0/29 (0%)	0
Nervous system disorders
Headache	6/29 (20.7%)	14	5/29 (17.2%)	5
Dizziness	5/29 (17.2%)	5	1/29 (3.4%)	1
Dysgeusia	3/29 (10.3%)	3	2/29 (6.9%)	2
Psychiatric disorders
Depression	5/29 (17.2%)	6	4/29 (13.8%)	4
Anxiety	3/29 (10.3%)	3	4/29 (13.8%)	4
Insomnia	4/29 (13.8%)	4	2/29 (6.9%)	2
Confusional state	1/29 (3.4%)	2	2/29 (6.9%)	2
Mental Disorder	0/29 (0%)	0	2/29 (6.9%)	2
Renal and urinary disorders
Proteinuria	6/29 (20.7%)	7	2/29 (6.9%)	2
Acute renal failure	2/29 (6.9%)	2	0/29 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/29 (27.6%)	10	4/29 (13.8%)	4
Epistaxis	4/29 (13.8%)	4	3/29 (10.3%)	3
Cough	3/29 (10.3%)	3	1/29 (3.4%)	1
Dysphonia	3/29 (10.3%)	3	0/29 (0%)	0
Exertional dyspnea	2/29 (6.9%)	2	1/29 (3.4%)	1
Pharyngolaryngeal pain	1/29 (3.4%)	1	2/29 (6.9%)	2
Hiccups	2/29 (6.9%)	2	0/29 (0%)	0
Pulmonary embolism	2/29 (6.9%)	2	0/29 (0%)	0
Acneiform dermatitis	22/29 (75.9%)	48	21/29 (72.4%)	27
Pruritus	5/29 (17.2%)	5	2/29 (6.9%)	2
Skin and subcutaneous tissue disorders
Skin disorder	1/29 (3.4%)	2	5/29 (17.2%)	5
Dry skin	4/29 (13.8%)	4	1/29 (3.4%)	1
Rash	2/29 (6.9%)	2	3/29 (10.3%)	4
Alopecia	4/29 (13.8%)	4	0/29 (0%)	0
Photosensitivity reaction	2/29 (6.9%)	2	0/29 (0%)	0
Vascular disorders
Deep vein thrombosis	4/29 (13.8%)	5	1/29 (3.4%)	1
Hypertension	2/29 (6.9%)	2	2/29 (6.9%)	3
Hypotension	2/29 (6.9%)	2	1/29 (3.4%)	1

Limitations/Caveats

Accrual on the trial was stopped earlier than planned due to insufficient efficacy in both arms.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. Sponsor may request publication delay up to 90 days to seek patent protection.