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

Metastatic Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01417000
• Other study ID #: ADU-CL-01
• Status: Completed
• Phase: Phase 2
• Start date: September 21, 2011
• Est. completion date: February 10, 2017

Study information

• Verified date: April 2018
• Source: Aduro Biotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT01468870

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: February 10, 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• GVAX Pancreas

• CRS-207

Drug:
• Cyclophosphamide

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital	Baltimore	Maryland
United States	National Cancer Institute	Bethesda	Maryland
United States	Duke University Medical Center	Durham	North Carolina
United States	Herbert Irving Comprehensive Cancer Center of Columbia University	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Virginia Mason Medical Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Aduro Biotech, Inc.	Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Epub 2004 Sep 13. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.

External Links

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