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Phase I EGFR BATs in Newly Diagnosed Glioblastoma

Study Purpose

This is a phase I trial using EGFR Bi-armed Activated T-cells (BATs) in combination with standard of care temozolomide (TMZ) and radiation (RT) in patients with glioblastoma (GBM). The purpose of the study is to determine a safe dose of EGFR BATs when given with standard of care therapy.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Histologically-confirmed newly diagnosed intracranial GBM or gliosarcoma. 2. Age ≥ 18 years. 3. Karnofsky Performance Status ≥ 60. 4. Be willing and able to provide written informed consent for the trial. 5. For patients with resection, CT/MRI with contrast must be performed within 72 hours following resection. Intraoperative post resection MRI is acceptable. No post surgery CT/MRI is required for patients who have received biopsy. 6. Females of childbearing potential, and males, must be willing to use an effective method of contraception. 7. Females of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days prior to apheresis. Absolute lymphocyte count ≥ 500/mm3, Absolute neutrophil count (ANC) ≥1,000 /mcL, Platelets ≥ 100,000 / mcL, Hemoglobin ≥ 9 g/dL (or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment), BUN ≤ 1.5 X upper limit of normal (ULN), Serum creatinine within the normal limits OR Measured or calculated creatinine clearance ≥60 mL/min/1.73m2, Serum total bilirubin ≤ 1.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 X ULN, Albumin >2.5 mg/dL, International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN, unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.i. Additional inclusion criteria for sub-cohort: MGMT unmethylated according to UVA pathology testing.

Exclusion Criteria:

1. Patients with a diagnosis of another malignancy within 3 years of being on-study. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Patients must not be on any treatment for another malignancy. 2. Patients with evidence of leptomeningeal dissemination or subependymal spread on initial MRI. 3. Patients with extracranial metastases. 4. Known hypersensitivity to cetuximab or other EGFR antibody. 5. Alpha 1,3 Galactose IgE ("alpha gal") test result outside of the reference range (indicating likely hypersensitivity to cetuximab) 6. Evidence of active bleeding or bleeding diathesis. 7. Cardiac Status: Patients will be ineligible for treatment on this protocol if (prior to protocol entry): There is a history of a recent (within one year) myocardial infarction or stroke. There is a current or prior history of angina/coronary symptoms requiring medications and/or evidence of depressed left ventricular function (LVEF < 45% by MUGA or ECHO). There is clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA or ECHO results). 8. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 9. Has received a live vaccine within 30 days of planned start of study therapy. 10. Has received any treatment for GBM besides surgery. 11. Females must not be breastfeeding. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 13. A patient may be excluded if, in the opinion of the treating clinician, the patient is not capable of being compliant.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03344250
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Virginia
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Camilo Fadul, MD
Principal Investigator Affiliation University of Virginia
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Unknown status
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma, Glioblastoma Multiforme
Additional Details

In addition to finding the safe dose of EGFR BATs, immune evaluations will be performed as delineated in the schedule of events to measure immune responses during all stages of treatment for GBM.

Arms & Interventions

Arms

Experimental: Main Study

Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. Participants will receive the first and second infusions of EGFR BATs on days 14 and 21 after finishing concurrent RT and TMZ and then receive an infusion on day 21 of the first six cycles of TMZ.

Experimental: Subcohort for MGMT unmethylated patients

Study participants will have cells collected by leukapheresis prior to initiating standard concurrent RT and TMZ. About 4 weeks after completion of RT/TMZ, participants will receive 8 weekly doses of EGFR BATs.

Interventions

Drug: - EGFR BATs with TMZ following SOC RT/TMZ

Standard of care: 6 weeks of RT and TMZ and 6 cycles of TMZ (150-200 mg/m2) on days 1-5 of each 28 day cycle Experimental: EGFR BATs 2 and 3 weeks after completing RT, and then on day 21 of each cycle of TMZ.

Drug: - Weekly EGFR BATs following SOC RT/TMZ

Standard of care: 6 weeks of RT and TMZ Experimental: 8 weekly doses of EGFR BATs following SOC RT and TMZ

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Samantha Brooks, Charlottesville, Virginia

Status

Address

Samantha Brooks

Charlottesville, Virginia, 22908