Phase I Study of Safety and Immunogenicity of ADU-623

NCT01967758 | Completed Phase 1

• 1 other identifier: 13-012A
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Astrocytic Tumors; Glioblastoma Multiforme; Anaplastic Astrocytoma; Brain Tumor

Keywords

Astrocytic Tumors; Glioblastoma Multiforme; Anaplastic Astrocytoma; Brain Tumor; Brain Cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Tumor response based on magnetic resonance imaging (MRI) exam

  24 months

• Immune Response

  91 Days

Study Arms (3)

Cohort 1

EXPERIMENTAL

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; Drug: Antibiotics

Cohort 2

EXPERIMENTAL

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.

Biological: Cohort 2; Drug: Antibiotics

Cohort 3

EXPERIMENTAL

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.

Biological: Cohort 3; Drug: Antibiotics

Interventions

Cohort 1 BIOLOGICAL

Four doses of IV ADU-623 at a dose of 3 x 10\^7cfu

Cohort 1

Cohort 2 BIOLOGICAL

Four doses of IV ADU-623 at a dose of 3 x 10\^8cfu

Cohort 2

Cohort 3 BIOLOGICAL

Four doses of IV ADU-623 at a dose of 3 x 10\^9cfu

Cohort 3

Antibiotics DRUG

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.

Also known as: Amoxicillin, Augmentin, trimethoprim / sulfamethoxazole, Bactrim

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Providence Health & Services: lead
• Aduro Biotech, Inc.: collaborator

Study Sites (1)

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Related Links

• Providence Cancer Center

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Brain Neoplasms

Interventions

KPNA1 protein, human; Anti-Bacterial Agents; Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Pharmaceutical Preparations; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Marka Crittenden, MD, PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2013
• First Posted: October 23, 2013
• Study Start: January 8, 2014
• Primary Completion: June 18, 2018
• Study Completion: August 15, 2018
• Last Updated: August 17, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data has been available from study start-up through the end of data analysis. Anticipated August 2018.
• Access Criteria: De-identified data will be made available to Aduro BioTech.

Locations

US (1)