Safety and Efficacy of Combination Listeria/GVAX Pancreas... | NCT02004262

Name	Class
Johns Hopkins University	OTHER

Label	Type	Description	Intervention Names
Primary Cohort: Cy/GVAX + CRS-207	Experimental	200 mg per square meter (mg/m^2) cyclophosphamide (Cy) administered by intravenous (IV) infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (GVAX, 5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 colony forming units [CFU]) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.	Biological: GVAX Pancreas Vaccine Biological: CRS-207 Drug: cyclophosphamide
Primary Cohort: CRS-207	Experimental	CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16. The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.	Biological: CRS-207
Primary Cohort: Chemotherapy	Active Comparator	Investigator's choice of one of the following: gemcitabine (1000 mg/m^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle. The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.

Name	Type	Description	Arm Group Labels	Other Names
GVAX Pancreas Vaccine	Biological		2nd-line Cohort: Cy/GVAX + CRS-207 Primary Cohort: Cy/GVAX + CRS-207	GVAX

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set)	OS was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs), with censoring at the date when 138 deaths were reached in the Primary Cohort in the FAS. Subjects without documentation of death at the time of final analysis were censored as of the date the subject was last known to be alive on/prior to the primary analysis data cut.	Subjects were followed from date of randomization to the date of death by any cause, whichever came first, assessed up to 32 months. Analysis conducted when 138 deaths reached in the Primary Cohort in the FAS.
Primary Cohort: OS (All Data, FAS)	For all treated subjects, OS was calculated using KM methods with 95% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis data cut.	Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.
2nd-line Cohort: OS (All Data, FAS)	For all treated subjects, OS was calculated using KM methods with 70% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis cut. 70% CIs were selected to provide an 80% probability to rule out differences in median survival less than -2.4 months between the 2nd-line Cohort: Chemotherapy arm and the 2nd-line Cohort: Cy/GVAX + CRS-207 and 2nd-line Cohort: CRS-207 arms, based upon the assumptions made in the statistical analysis plan (SAP).	Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen	Safety was assessed based upon the number of adverse events (AEs) that occurred in the FAS of each treatment arm, including serious AEs and total AEs. Total AEs included both serious and non-serious AEs.	From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease
2nd line, 3rd line or greater
At least 18 years of age
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Anticipated life expectancy >12 weeks
For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. A barrier method of contraception must be employed by all subjects (male and female), regardless of other methods.
Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

Allergy to both penicillin & sulfa or suspected hypersensitivity to granulocyte-macrophage colony stimulating factor (GM-CSF), dimethyl sulfoxide, fetal bovine serum, trypsin, yeast, glycerol or other component of the therapy options
Known history or evidence of brain metastases, immunodeficiency disease or immunocompromised state or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
Have prosthetic heart valves, major implant or device placed in the last 12 months or history of infection with implant/device that cannot be easily removed
Rapidly progressing disease
Clinically significant and/or malignant pleural effusion
Received prior GVAX pancreas vaccine or CRS-207
Major surgery or significant traumatic injury (or unhealed surgical wounds) occurring within 28 days prior to receiving study drug, or planned surgery requiring general anesthesia
Infection with HIV or hepatitis B or C at screening
Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
Pregnant or breastfeeding
Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen
Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures

Facility	Status	City	State	ZIP	Country	Contacts
Scottsdale Healthcare Research Institute		Scottsdale	Arizona	85258	United States
University California San Diego Moores Cancer Center

PubMed Identifier	Type	Citation	Retractions
15365184	Background	Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W, Cook DN, Portnoy DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.
22147941	Background

Label	URL
The Pancreatic Cancer Action Network's Patient \& Liaison Services (PALS) program provides patients and families with information and resources at no cost. Visit www.pancan.org, call 877-272-6226 or email pals@pancan.org for information.	View source

ID	Title	Description
FG000	Primary Cohort: Cy/GVAX + CRS-207	200 mg per square meter (mg/m^2) cyclophosphamide (Cy) administered by intravenous (IV) infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (GVAX, 5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 colony forming units [CFU]) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. The Primary Cohort comprised those subjects who failed at least 1 gemcitabine-based regimen administered for pancreatic cancer in any setting and failed at least 2 prior chemotherapy regimens administered for pancreatic cancer in the metastatic setting.

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

Primary Cohort: Overall Survival (OS) Censored at 138 Deaths (ITT Set)

OS was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs), with censoring at the date when 138 deaths were reached in the Primary Cohort in the FAS. Subjects without documentation of death at the time of final analysis were censored as of the date the subject was last known to be alive on/prior to the primary analysis data cut.

Analysis based on subjects in the Primary Cohort in the intent-to-treat (ITT) set. The ITT set is the analysis population that included all randomized study subjects.

Posted

Median

95% Confidence Interval

months

Subjects were followed from date of randomization to the date of death by any cause, whichever came first, assessed up to 32 months. Analysis conducted when 138 deaths reached in the Primary Cohort in the FAS.

ID	Title	Description
OG000	Primary Cohort: Cy/GVAX + CRS-207
OG001	Primary Cohort: CRS-207
OG002	Primary Cohort: Chemotherapy

Units	Counts
Participants	OG00073 OG00168 OG00272

Title

Denominators

Categories

Title	Measurements
	OG0003.8(2.9 to 5.3) OG0015.4(4.2 to 6.9) OG0024.6(4.2 to 5.8)

Primary

Primary Cohort: OS (All Data, FAS)

For all treated subjects, OS was calculated using KM methods with 95% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis data cut.

Analysis based on subjects in the Primary Cohort in the FAS.

Posted

Median

95% Confidence Interval

months

Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.

ID	Title	Description
OG000	Primary Cohort: Cy/GVAX + CRS-207
OG001	Primary Cohort: CRS-207
OG002	Primary Cohort: Chemotherapy

Units	Counts
Participants	OG000

Primary

2nd-line Cohort: OS (All Data, FAS)

For all treated subjects, OS was calculated using KM methods with 70% CIs. Subjects without documentation of death at the time of the analysis were censored as of the date the subject was last known to be alive on/prior to the final analysis cut. 70% CIs were selected to provide an 80% probability to rule out differences in median survival less than -2.4 months between the 2nd-line Cohort: Chemotherapy arm and the 2nd-line Cohort: Cy/GVAX + CRS-207 and 2nd-line Cohort: CRS-207 arms, based upon the assumptions made in the statistical analysis plan (SAP).

Analysis based on subjects in the 2nd-line Cohort in the FAS.

Posted

Median

70% Confidence Interval

months

Subjects followed for survival from date of randomization until lost to follow-up, withdrawal of consent, or death, whichever came first, assessed up to 32 months.

ID	Title	Description
OG000	2nd-line Cohort: Cy/GVAX + CRS-207
OG001	2nd-line Cohort: CRS-207
OG002	2nd-line Cohort: Chemotherapy

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events in Each Treatment Arm Treatment Regimen

Safety was assessed based upon the number of adverse events (AEs) that occurred in the FAS of each treatment arm, including serious AEs and total AEs. Total AEs included both serious and non-serious AEs.

Analysis conducted for the FAS of each study arm.

Posted

Count of Participants

Participants

From the start of the first study drug administration on Day 1, Week 1, through 28 days after the last study drug dose, assessed up to 32 months from the date of randomization.

ID	Title	Description
OG000	Pooled Cohort: Cy/GVAX + CRS-207	200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. Participants from both the Primary and 2nd-Line Cohorts receiving at least 1 Cy/GVAX + CRS-207 treatment were combined to form the Pooled Cohort.
OG001	Pooled Cohort: CRS-207	CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16. Participants from both the Primary and 2nd-Line Cohorts receiving at least 1 CRS-207 treatment were combined to form the Pooled Cohort.
OG002	Pooled Cohort: Chemotherapy

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected94 at risk EG0014 affected87 at risk EG0022 affected54 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0012 affected87 at risk EG0021 affected54 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0012 affected87 at risk EG0020 affected54 at risk
Colitis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Ileus	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0021 affected54 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0012 affected87 at risk EG0020 affected54 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0022 affected54 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0021 affected54 at risk
Ascites	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Gastritis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0021 affected54 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Disease progression	General disorders	MedDRA 17.0	Systematic Assessment	EG00013 affected94 at risk EG0015 affected87 at risk EG0022 affected54 at risk
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Death	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Asthenia	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Device dislocation	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0021 affected54 at risk
Bacteraemia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Fungal oesophagitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0021 affected54 at risk
Herpes zoster	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Influenza	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Klebsiella sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Lung infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Encephalopathy	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Memory impairment	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Spinal cord compression	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Syncope	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected94 at risk EG0012 affected87 at risk EG0020 affected54 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0013 affected87 at risk EG0020 affected54 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0022 affected54 at risk
Haemorrhage	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Hypertension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Hypotension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Venous thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Cardiac arrest	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Mental status changes	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Confusional state	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Delirium	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Hallucination	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Gastrointestinal anastomotic complication	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Blood glucose decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Weight decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Oliguria	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Chills	General disorders	MedDRA 17.0	Systematic Assessment	EG00059 affected94 at risk EG00181 affected87 at risk EG0025 affected54 at risk
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG00051 affected94 at risk EG00158 affected87 at risk EG0029 affected54 at risk
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG00050 affected94 at risk EG00138 affected87 at risk EG00226 affected54 at risk
Vaccination site erythema	General disorders	MedDRA 17.0	Systematic Assessment	EG00077 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vaccination site induration	General disorders	MedDRA 17.0	Systematic Assessment	EG00053 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vaccination site pain	General disorders	MedDRA 17.0	Systematic Assessment	EG00053 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vaccination site oedema	General disorders	MedDRA 17.0	Systematic Assessment	EG00051 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vaccination site pruritus	General disorders	MedDRA 17.0	Systematic Assessment	EG00049 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Vaccination site bruising	General disorders	MedDRA 17.0	Systematic Assessment	EG00025 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG00015 affected94 at risk EG0016 affected87 at risk EG0022 affected54 at risk
Disease progression	General disorders	MedDRA 17.0	Systematic Assessment	EG00013 affected94 at risk EG0015 affected87 at risk EG0022 affected54 at risk
Pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0017 affected87 at risk EG0022 affected54 at risk
Asthenia	General disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0013 affected87 at risk EG0022 affected54 at risk
Vaccination site vesicles	General disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00042 affected94 at risk EG00144 affected87 at risk EG00229 affected54 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00032 affected94 at risk EG00132 affected87 at risk EG00213 affected54 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00030 affected94 at risk EG00133 affected87 at risk EG00212 affected54 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00025 affected94 at risk EG00121 affected87 at risk EG00210 affected54 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG00012 affected94 at risk EG00118 affected87 at risk EG00220 affected54 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0014 affected87 at risk EG0024 affected54 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0009 affected94 at risk EG0014 affected87 at risk EG0022 affected54 at risk
Flatulence	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0015 affected87 at risk EG0022 affected54 at risk
Ascites	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0013 affected87 at risk EG0021 affected54 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0015 affected87 at risk EG0021 affected54 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0012 affected87 at risk EG0021 affected54 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG00024 affected94 at risk EG00116 affected87 at risk EG00219 affected54 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0007 affected94 at risk EG00110 affected87 at risk EG0027 affected54 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG00013 affected94 at risk EG0017 affected87 at risk EG0023 affected54 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0016 affected87 at risk EG0025 affected54 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0019 affected87 at risk EG0022 affected54 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0016 affected87 at risk EG0022 affected54 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0014 affected87 at risk EG0021 affected54 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0013 affected87 at risk EG0020 affected54 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0011 affected87 at risk EG0020 affected54 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG00017 affected94 at risk EG00120 affected87 at risk EG0021 affected54 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG00018 affected94 at risk EG00113 affected87 at risk EG0022 affected54 at risk
Alanine aminotransferase increased	Investigations	MedDRA 17.0	Systematic Assessment	EG00012 affected94 at risk EG00116 affected87 at risk EG0021 affected54 at risk
Weight decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG00010 affected94 at risk EG0016 affected87 at risk EG0023 affected54 at risk
Blood bilirubin increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0013 affected87 at risk EG0022 affected54 at risk
Blood albumin decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0017 affected87 at risk EG0020 affected54 at risk
Lymphocyte count decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0007 affected94 at risk EG0014 affected87 at risk EG0021 affected54 at risk
Blood creatinine increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0014 affected87 at risk EG0020 affected54 at risk
Blood sodium decreased	Investigations	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0014 affected87 at risk EG0020 affected54 at risk
International normalised ratio increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0010 affected87 at risk EG0020 affected54 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG00019 affected94 at risk EG00118 affected87 at risk EG0029 affected54 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG00012 affected94 at risk EG00110 affected87 at risk EG0024 affected54 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0012 affected87 at risk EG0020 affected54 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0011 affected87 at risk EG0023 affected54 at risk
Hypotension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG00018 affected94 at risk EG00118 affected87 at risk EG0020 affected54 at risk
Hypertension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG00010 affected94 at risk EG00113 affected87 at risk EG0020 affected54 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0011 affected87 at risk EG0023 affected54 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG00018 affected94 at risk EG00113 affected87 at risk EG0023 affected54 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0007 affected94 at risk EG00111 affected87 at risk EG0020 affected54 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0017 affected87 at risk EG0021 affected54 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0015 affected87 at risk EG0021 affected54 at risk
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG00018 affected94 at risk EG00119 affected87 at risk EG0022 affected54 at risk
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0007 affected94 at risk EG00110 affected87 at risk EG0023 affected54 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0011 affected87 at risk EG0024 affected54 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG00011 affected94 at risk EG0015 affected87 at risk EG0021 affected54 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected94 at risk EG0014 affected87 at risk EG0027 affected54 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG00211 affected54 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0011 affected87 at risk EG0021 affected54 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0014 affected87 at risk EG0020 affected54 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0010 affected87 at risk EG0024 affected54 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0008 affected94 at risk EG0017 affected87 at risk EG0026 affected54 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0013 affected87 at risk EG0022 affected54 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0006 affected94 at risk EG0013 affected87 at risk EG0021 affected54 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0015 affected87 at risk EG0020 affected54 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected94 at risk EG0010 affected87 at risk EG0023 affected54 at risk
Tachycardia	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG00013 affected94 at risk EG00115 affected87 at risk EG0022 affected54 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0016 affected87 at risk EG0021 affected54 at risk
Insomnia	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0009 affected94 at risk EG0015 affected87 at risk EG0022 affected54 at risk
Confusional state	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0014 affected87 at risk EG0022 affected54 at risk
Anxiety	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected94 at risk EG0015 affected87 at risk EG0023 affected54 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0013 affected87 at risk EG0024 affected54 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 affected94 at risk EG0010 affected87 at risk EG0023 affected54 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0005 affected94 at risk EG0013 affected87 at risk EG0021 affected54 at risk

ID	Term
D004358	Drug Therapy
D003520	Cyclophosphamide

ID	Term
D013812	Therapeutics
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds

ID	Title	Description
BG000	Primary Cohort: Cy/GVAX + CRS-207
BG001	Primary Cohort: CRS-207
BG002	Primary Cohort: Chemotherapy
BG003	2nd-line Cohort: Cy/GVAX + CRS-207
BG004	2nd-line Cohort: CRS-207
BG005	2nd-line Cohort: Chemotherapy
BG006	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	Pooled Cohort: Cy/GVAX + CRS-207	200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1 and 4; GVAX pancreas vaccine (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1 and 4; CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 7, 10, 13, 16. Participants from both the Primary and 2nd-Line Cohorts receiving at least 1 Cy/GVAX + CRS-207 treatment were combined to form the Pooled Cohort.	88	94	44	94	94	94
EG001	Pooled Cohort: CRS-207	CRS-207 (1 × 10e9 CFU) administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16. Participants from both the Primary and 2nd-Line Cohorts receiving at least 1 CRS-207 treatment were combined to form the Pooled Cohort.	82	87	32	87	87	87
EG002	Pooled Cohort: Chemotherapy	Investigator's choice of one of the following: gemcitabine (1000 mg/m^2) administered by IV infusion on Days 1, 8, and 15 of a 28-day cycle; capecitabine (1000 mg/m^2) administered orally twice a day on Days 1 through 14 of a 21-day cycle; fluorouracil with or without leucovorin (2400 mg^m2) administered by IV infusion over 46 hours on Days 1 and 15 of a 28-day cycle; irinotecan (150 mg/m^2) administered by IV infusion on Days 1 and 15 of a 28-day cycle; or erlotinib (100 mg) administered orally once a day for a 21-day cycle. Participants from both the Primary and 2nd-Line Cohorts receiving at least 1 chemotherapy treatment were combined to form the Pooled Cohort.	51	54	15	54	51	54