Clinical trial NCT01417000: Safety and Efficacy of Combination Listeria/GVAX Immunotherapy in Pancreatic Cancer
Official title: A Phase 2, Randomized, Multicenter, Open-Label Study of the Efficacy and Immune Response of the Sequential Administration of GVAX Pancreas Vaccine Alone or Followed by CRS-207 in Adults With Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: Cancer
Cancer vaccine
Listeria monocytogenes
Listeria-based vaccines
GVAX
Cyclophosphamide
Cytoxan
T regulatory cells
Heterologous Prime-Boost
Immunotherapy
Mesothelin
Pancreatic cancer
Lead sponsor: Aduro Biotech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Johns Hopkins University
First posted: 2011-08-16
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall Survival (OS) in Subjects Receiving Test Treatments (FAS)
timeFrame: Subjects were followed from the date of randomization to the date of death or discontinuation, whichever came first, assessed up to 60 months.
Secondary outcomes:
measure: To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen
timeFrame: 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.
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
state: Maryland
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center of Columbia University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Johns Hopkins University
name: Dung T Le, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.