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

NCT01417000 | Completed Phase 2 Results DMC

• 1 other identifier: ADU-CL-01
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 10

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To Assess Safety of the Cyclophosphamide, GVAX Pancreas Vaccine, and CRS-207 Treatment Regimen

  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.

Study Arms (2)

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.

Biological: GVAX Pancreas; Biological: CRS-207; Drug: Cyclophosphamide

Cy/GVAX

EXPERIMENTAL

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; Drug: Cyclophosphamide

Interventions

GVAX Pancreas BIOLOGICAL

Also known as: GVAX

Cy/GVAX; Cy/GVAX + CRS-207

CRS-207 BIOLOGICAL

Cy/GVAX + CRS-207

Cyclophosphamide DRUG

Also known as: Cytoxan, Cy

Cy/GVAX; Cy/GVAX + CRS-207

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aduro Biotech, Inc.: lead
• Johns Hopkins University: collaborator

Study Sites (10)

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Herbert Irving Comprehensive Cancer Center of Columbia University

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related 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. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.

  PMID: 15365184 BACKGROUND

• 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.

  PMID: 18316569 BACKGROUND

• 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.

  PMID: 22595054 BACKGROUND

• 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.

  PMID: 25584002 BACKGROUND

Related Links

• For more information, please click here to visit Aduro's website.

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Corporate Communications
• Organization: Aduro Biotech, Inc.

510-848-4400

Study Officials

• Dung T Le, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2011
• First Posted: August 16, 2011
• Study Start: September 21, 2011
• Primary Completion: October 1, 2016
• Study Completion: February 10, 2017
• Last Updated: May 8, 2018
• Results First Posted: May 8, 2018

Record last verified: 2018-04

Locations

US (10)