Phase I Study of Safety and Immunogenicity of ADU-623

Phase I Study of Safety and Immunogenicity of ADU-623, a Live-attenuated Listeria Monocytogenes Strain (ΔactA/ΔinlB) Expressing the EGFRvIII-NY-ESO-1 Vaccine, in Patients With Treated and Recurrent WHO Grade III/IV Astrocytomas

This is a study for patients with brain tumors called astrocytic tumors. The study will enroll patients who have received standard treatment. The study will test a vaccine called ADU-623. ADU-623 has not been tested in humans before, so the goal of this study is to see if ADU-623 can be given safely to brain cancer patients and what is the better dose to give patients among the three doses that planned to be tested. This study will also evaluate the length of time before patients' cancer worsens and if ADU-623 helps patients to live longer. The study will also measure the body's immune system response to ADU-623.

Study Overview

• Status: Completed
• Conditions: Brain Tumor; Glioblastoma Multiforme; Anaplastic Astrocytoma; Astrocytic Tumors
• Intervention / Treatment: Biological: Cohort 1; Drug: Antibiotics; Biological: Cohort 2; Biological: Cohort 3

Detailed Description

This Phase I clinical trial will examine the safety, tolerability and immunogenicity of a novel vaccine approach using a live-attenuated strain of Listeria monocytogenes expressing EGFRvIII and NY-ESO-1 antigens to induce proliferation of memory and effector T cells with the overall goal of promoting an immune response against high-grade astrocytic tumors.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a pathologic diagnosis of WHO Grade III or Grade IV astrocytic tumors that have completed standard of care or with radiographic evidence of progression following standard of care.
• Tumor tissue blocks available to perform both EGFRvIII and NY-ESO-1 testing
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky Performance Status (KPS) 70-100
• Age 18 years or above
• Have a life expectancy of more than 12 weeks
• Laboratory values (performed within 5 days) within designated range.
• For women and men of childbearing potential, an acceptable method of highly effective contraception
• Ability to give informed consent and comply with the protocol.

Exclusion Criteria:

• Have a known allergy to both penicillin and sulfa
• Have artificial (prosthetic) joint(s), orthopedic screw(s), metal plate(s) or other exogenous implant(s) or device(s) that cannot be easily removed (i.e., prosthetic heart valves).
• Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.
• Have radiographic or clinically significant pleural effusion.
• Receipt of prophylactic vaccine within 28 days of study treatment.
• 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).
• History of allergy to yeast or any other component of the ADU-623 vaccine (e.g., glycerol).
• Have an immunodeficiency disease or immunocompromised state (e.g., use of immunosuppressive agents; chemotherapy or radiation therapy within 14 days of study treatment).
• Have had major surgery or significant traumatic injury occurring within 28 days before treatment administration or anticipated surgery or procedure requiring general anesthesia during study participation (including 28 days after last dose of ADU-623).
• Use of more than 4 grams per day of acetaminophen.
• Have received an investigational product within 28 days of study treatment or planned to receive within 28 days after vaccine administration.
• Have an unhealed surgical wound.
• Have clinically significant heart disease (such as uncontrolled angina, myocardial infarction with the last 3 months, congestive heart failure of New York Heart Association III or IV).
• Have valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis.
• Have an intercurrent illness that is either life-threatening or of clinical significance such that it might limit compliance with study requirements including, but not limited to, ongoing or active infection, metabolic or neurological disease, peripheral vascular disease or psychiatric illness.
• Have insufficient peripheral venous access to permit completion of the study dosing and compliance with study phlebotomy regimen.
• Have received a diagnosis of HIV, HCV, or HBV (patients with hepatitis C antibody positive may be enrolled if they are confirmed with negative viral load at screening).
• Have an active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment.
• Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in protocol.
• Pregnant or lactating women, as treatment has unknown effect on the embryo or child.
• Patients requiring chronic corticosteroid use will be excluded as this may mask toxic effects related to the vaccine and may prevent the development of effective immune responses following vaccination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients in Cohort 1 will receive ADU-623 at a dose of 3 x 10^7cfu by intravenous infusion (IV) over 2 hours on Day 0, Day 21, Day 42, and Day 63. Each dose is followed by a 3-day course or antibiotics. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.	Biological: Cohort 1; Four doses of IV ADU-623 at a dose of 3 x 10^7cfu; Drug: Antibiotics; A 3-day course of oral amoxicillin (500 mg three times per day) or trimethoprim/sulfamethoxazole in penicillin-allergic patients (160 mg trimethoprim / 800mg sulfamethoxazole at 12 hour intervals) will be initiated for each patient 3 days following each dose of ADU-623. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.; Other Names: Augmentin; Amoxicillin; Bactrim; trimethoprim / sulfamethoxazole
Experimental: Cohort 2; Patients in Cohort 2 will receive ADU-623 at a dose of 3 x 10^8cfu by intravenous infusion (IV) over 2 hours on Day 0, Day 21, Day 42, and Day 63. Each dose is followed by a 3-day course or antibiotics. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.	Drug: Antibiotics; A 3-day course of oral amoxicillin (500 mg three times per day) or trimethoprim/sulfamethoxazole in penicillin-allergic patients (160 mg trimethoprim / 800mg sulfamethoxazole at 12 hour intervals) will be initiated for each patient 3 days following each dose of ADU-623. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.; Other Names: Augmentin; Amoxicillin; Bactrim; trimethoprim / sulfamethoxazole; Biological: Cohort 2; Four doses of IV ADU-623 at a dose of 3 x 10^8cfu
Experimental: Cohort 3; Patients in Cohort 3 will receive ADU-623 at a dose of 3 x 10^9cfu by intravenous infusion (IV) over 2 hours on Day 0, Day 21, Day 42, and Day 63. Each dose is followed by a 3-day course or antibiotics. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.	Drug: Antibiotics; A 3-day course of oral amoxicillin (500 mg three times per day) or trimethoprim/sulfamethoxazole in penicillin-allergic patients (160 mg trimethoprim / 800mg sulfamethoxazole at 12 hour intervals) will be initiated for each patient 3 days following each dose of ADU-623. Patients will receive a 7-day course of antibiotics starting at the end of treatment visit.; Other Names: Augmentin; Amoxicillin; Bactrim; trimethoprim / sulfamethoxazole; Biological: Cohort 3; Four doses of IV ADU-623 at a dose of 3 x 10^9cfu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	The primary objective of this trial is to determine the maximum tolerated dose (MTD)(up to a dose of 1x10^9 cfu IV) and characterize the safety profile of ADU-623 vaccine in patients with recurrent WHO Grade III/IV Astrocytomas. The MTD will be defined as the highest dose at which none or one out of 6 patients experiences a dose-limiting toxicity (DLT) that is possibly or probably related to the vaccine.	91 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response based on magnetic resonance imaging (MRI) exam	The efficacy of therapy on tumor burden and time to progression will be assessed by MRI.	24 months
Immune Response	Innate and adaptive immunologic response will be assessed by looking at changes in cytokines and changes in cellular and humoral immunity.	91 Days

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Aduro Biotech, Inc.
• Investigators: Principal Investigator: Marka Crittenden, MD, PhD, Providence Health & Services

Publications and helpful links

Helpful Links

• Providence Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2014
• Primary Completion (Actual): June 18, 2018
• Study Completion (Actual): August 15, 2018

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 23, 2013

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Brain Tumor; Glioblastoma Multiforme; Immunotherapy; Brain Cancer; Anaplastic Astrocytoma; Astrocytic Tumors
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Glioblastoma; Brain Neoplasms; Astrocytoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; beta-Lactamase Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Anti-Bacterial Agents; Amoxicillin; Trimethoprim; Sulfamethoxazole; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: 13-012A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated by this study will be shared with the collaborator, Aduro BioTech.
• IPD Sharing Time Frame: Data has been available from study start-up through the end of data analysis. Anticipated August 2018.
• IPD Sharing Access Criteria: De-identified data will be made available to Aduro BioTech.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR