Anti-CD3 X Anti-Erbitux® Armed Activated T Cells (Phase Ib) For Gastrointestinal (GI Cancer)

Study Overview

Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer)

The purpose of this research study is for the participant to give their own T cells (a type of blood cell in the body that can fight infections and possibly cancer) to them after they have been removed, grown in a lab, and then coated with an experimental drug. This study will determine the highest dose of EGFR2Bi coated T cells that can be given without causing severe side effects. Initially a group of 3 participants will receive the same dose of study drug. If no serious side effects occur, the next group of participants will receive a slightly higher dose of study agent. The following groups of participants will receive higher doses of the study drug until a dose is reached where there are unacceptable side effects and maximum tolerated dose is found, or the planned highest dose level is reached with no side effects.

The purpose of this study is to determine in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi armed activated T cells (aATC), after chemotherapy, for patients with advanced colorectal and pancreatic cancer

Colorectal Cancer
Cancer of Pancreas
Pancreatic Neoplasm
Malignant Neoplasm of Large Intestine
Malignant Tumor of Colon
Colon Carcinoma
Cancer of Colon
Pancreatic Cancer

DRUG: FOLFOX6
BIOLOGICAL: EGFRBi armed ATC Infusions

2011-025

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-08-17	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-05-04
First Submitted that Met QC Criteria 2011-08-19	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-05-06
First Posted (ACTUAL) 2011-08-22	Results First Posted N/A	Last Verified 2023-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: FOLFOX6 & EGFRBi armed ATC Infusions FOLFOX6: IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, P	DRUG: FOLFOX6 IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line) BIOLOGICAL: EGFRBi armed ATC Infusions Armed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subse

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: FOLFOX6 & EGFRBi armed ATC Infusions

FOLFOX6: IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, P

DRUG: FOLFOX6

IV administration of 85 mb/m(2) oxaliplatin and 400 mg/m(2) leucovorin over 120 mins, followed by 400 mg/m(2) 5-fluorouracil (FU) bolus then 2400 mg/m(2) 5-FU as a 46 hr infusion. All patients must have central intravenous acess (e.g. mediport, PICC line)

BIOLOGICAL: EGFRBi armed ATC Infusions

Armed ATC will be infused intravenously (IV) with the rate of infusion based on the endotoxin content of the product. All patients will be observed for at least 4 hours after an infusion. Armed ATC infusions will begin 3 weeks after chemotherapy and subse

Primary Outcome Measures	Measure Description	Time Frame
Determining in a dose-escalation phase Ib trial the safety of 3 infusions of EGFR2Bi aATC, and a booster infusion after 3 months, for patients with advanced colorectal or pancreatic cancer.	Participants will be assessed for changes in lab values (CBC, Sodium, potassium, calcium, magnesium, chloride, bicarbonate, glucose,BUN, creatinine, total Protein, albumin, total bilirubin, ALP, AST,ALT, CEA or CA 19-9.	4 wks after chemo, prior to ATC infusion #2; 1 wk later prior to ATC infusion #3; Wks 2, 4 & 9 post ATC infusion #3; Wk 8 post ATC #4 (booster)

Secondary Outcome Measures	Measure Description	Time Frame
Determining whether IMT enhances anti-tumor immunity;Cytokine resp., phenotypic markers, anti-tumor cytotoxicity, in vivo and in vitro specific anti-tumor antibody prod. & molecular signaling markers of T-cell activation assessed before chemo & after IMT	Immune studies: Serum cytokine responses will be quantified focus on the levels of those factors known to be important regulators of T cell responses. Phenotype analysis will measure the percent of T, B, NKT and NK cells in peripheral blood mononuclear cell (PBMC) and tumor-infiltrating lymphocyte (TIL) samples. T cell proportions would be further analyzed by subset (CD4, CD8, CD25+). Cytotoxicity is measured in percentage in PBMC.	3 weeks after chemo prior to ATC infusion #1; At wks 4(ATC #2) & 5 (ATC #3) post chemo; wks 2 , 4 & 9 post ATC #3 infusion; Day of ATC #4 (booster infusion), then wks 2, 4 & 8; & mon 6 and 1yr post ATC #4 (booster infusion)
Determining the tumor response rate	CT or PET Scan	Approximately every 8 weeks to until 1 year
Overall Survival	CT or PET Scan	Approximately every 8 weeks to until 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histological or cytological proof of colorectal or pancreatic adenocarcinoma
Must have metastatic colorectal cancer or pancreatic cancer with stable disease after first line chemotherapy or patients with colorectal or pancreatic cancer who have progressed with standard chemotherapy options*
Standard chemotherapy for metastatic colorectal cancer include 5-FU/capecitabine with either oxaliplatin or irinotecan based regimen with or without bevacizumab or cetuximab.
Standard chemotherapy for metastatic pancreatic cancer include gemzar based regimen or FOLFIRINOX (5-FU, oxaliplatin, and irinotecan)
Prior cetuximab, panitumumab, or other monoclonal antibody therapy allowed if given 28 days prior to the 1st infusion of armed T cells
Absolute Neutrophil Count (ANC) ≥ 1,000/mm3
Lymphocyte count ≥ 400/mm3
Platelet Count ≥ 50,000/mm3
Hemoglobin ≥ 8 g/dL
Serum Creatinine < 2.0 mg/dl, Creatinine Clearance ≥50 ml/mm (can be calculated)
Total Bilirubin ≤ 2 mg/dl (biliary stent is allowed)
SGPT and SGOT < 5.0 times normal
LVEF ≥ 45% at rest (MUGA or Echo)
Pulse Oximetry of >88%
Age ≥ 18 years at the time of consent
Written informed consent and HIPAA authorization for release of personal health information
Females of childbearing potential, and males, must be willing to use an effective method of contraception
Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy
KPS ≥ 70% or SWOG Performance Status 0 or 1

Any chemotherapy related toxicities from prior treatment.(> grade I per CTCAE v4.0
Known hypersensitivity to cetuximab or other EGFR antibody
Treatment with any investigational agent within 14 days prior to being registered for protocol therapy Protocol version: 07/13/2011 8
Symptomatic brain metastasis
Chronic treatment with systemic steroids or another immuno-suppressive agent
Serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
Active liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
HIV infection
Positive HbsAg
Positive Hepatitis C
Active bleeding or a pathological condition that is associated with a high risk of bleeding
Uncontrolled systemic disease like active infections
Nonmalignant medical illnesses that are uncontrolled or a controlled illness that may be jeopardized by the treatment with protocol therapy
Females must not be breastfeeding
Patient may be excluded if, in the opinion of the PI and investigator team, the patient is not capable of being compliant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Anthony Shields, M.D. PhD, Barbara Ann Karmanos Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Lum LG, Thakur A, Choi M, Deol A, Kondadasula V, Schalk D, Fields K, Dufrense M, Philip P, Dyson G, Aon HD, Shields AF. Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients. Oncoimmunology. 2020 Jun 10;9(1):1773201. doi: 10.1080/2162402X.2020.1773201.

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Clinical Trial Record