Safety And Efficacy Of Combination Listeria/GVAX Immunotherapy In Pancreatic Cancer

Study Overview

Safety and Efficacy of Combination Listeria/GVAX Immunotherapy in Pancreatic Cancer

Test the safety, immune response and efficacy of GVAX pancreas vaccine (with cyclophosphamide) and CRS-207 compared to GVAX pancreas vaccine (with cyclophosphamide) alone in adults who have failed or refused prior treatment for metastatic pancreatic cancer.

N/A

Metastatic Pancreatic Cancer

BIOLOGICAL: GVAX Pancreas
BIOLOGICAL: CRS-207
DRUG: Cyclophosphamide

ADU-CL-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-08-10	Results First Submitted 2018-04-06	Last Update Submitted that met QC Criteria 2018-04-06
First Submitted that Met QC Criteria 2011-08-12	Results First Submitted that Met QC Criteria 2018-04-06	Last Update Posted (ACTUAL) 2018-05-08
First Posted (ACTUAL) 2011-08-16	Results First Posted 2018-05-08	Last Verified 2018-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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 col	BIOLOGICAL: GVAX Pancreas BIOLOGICAL: CRS-207 DRUG: Cyclophosphamide
EXPERIMENTAL: Cy/GVAX 200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16; GVAX (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1, 4, 7, 10, 13, 16.	BIOLOGICAL: GVAX Pancreas BIOLOGICAL: CRS-207 DRUG: Cyclophosphamide

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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 col

BIOLOGICAL: GVAX Pancreas

BIOLOGICAL: CRS-207

DRUG: Cyclophosphamide

EXPERIMENTAL: Cy/GVAX

200 mg/m^2 Cy administered by IV infusion on Day 1 of Weeks 1, 4, 7, 10, 13, 16; GVAX (5 × 10e8 cells) administered by intradermal injection on Day 2 of Weeks 1, 4, 7, 10, 13, 16.

BIOLOGICAL: GVAX Pancreas

BIOLOGICAL: CRS-207

DRUG: Cyclophosphamide

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival (OS) in Subjects Receiving Test Treatments (FAS)	For all treated subjects, OS was defined as the time between the date of randomization and the date of death or censoring, and was estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). Subjects without documentation of death at the time of the final analysis were censored using the date the subject was last known to be alive. Per the study protocol, following an Interim Analysis (IA), subjects in the Cy/GVAX arm were offered rollover to Cy/GVAX + CRS-207 arm. 3 subjects rolled over to the Cy/GVAX + CRS-207 arm (rollover subjects). These rollover subjects were censored at the day prior to the first rollover treatment dose date, and were included for analysis in the Cy/GVAX arm. Additionally, 2 subjects originally treated per the Cy/GVAX + CRS-207 arm discontinued treatment and entered follow-up, but following IA were re-treated per the Cy/GVAX + CRS-207 arm regimen. Data from these "re-treated subjects" were included in the Cy/GVAX + CRS-207 arm analysis.	Subjects were followed from the date of randomization to the date of death or discontinuation, whichever came first, assessed up to 60 months.

Secondary Outcome Measures	Measure Description	Time Frame
To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 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. AEs reported for the Cy/GVAX + CRS-207 arm (FAS) include the 61 treated subjects initially assigned to this arm plus AEs occurring on/after the first rollover dose date for the 3 Cy/GVAX rollover subjects. AEs reported for the Cy/GVAX arm (FAS) include treated subjects initially assigned to this arm but exclude AEs for rollover subjects occurring on/after the first rollover dose date.	Starting with administration of first investigational drug product through 28 days after final study treatment, assessed up to 60 months from the date of randomization.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required. (Subjects with mixed histology will be included if the predominant component is adenocarcinoma. Subjects must have metastatic disease.)
Have received or refused at least one chemotherapy regimen
At least 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Anticipated life expectancy of >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.)
Be willing and able to give written informed consent, and be able to comply with all study procedures
Have adequate organ function as defined by specified laboratory values

Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions
Known history or evidence of brain metastases
Have any evidence of hepatic cirrhosis or clinical or radiographic ascites
Have clinically significant and/or malignant pleural effusion
Known or suspected hypersensitivity to any component of GVAX Pancreas vaccine or CRS-207, or known allergy to both penicillin and sulfa
Received an investigational product within 28 days of study treatment or planned to receive within 28 days after vaccine administration
Used any systemic steroids within 28 days of study treatment
Use more than 3 g/d of acetaminophen
Prosthetic joint or other artificial implant or device that cannot be easily removed (there are some exceptions)
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
Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment
Be 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Johns Hopkins University

Investigators

PRINCIPAL_INVESTIGATOR: Dung T Le, MD, Johns Hopkins University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, Tartakovsky I, Nemunaitis J, Le D, Sugar E, Hege K, Jaffee E. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008 Mar 1;14(5):1455-63. doi: 10.1158/1078-0432.CCR-07-0371.
Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.
Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T Jr, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. doi: 10.1200/JCO.2014.57.4244. Epub 2015 Jan 12.

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