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

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 1

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

Treatments: Drug: FOLFOX6; Biological: EGFRBi armed ATC Infusions

Study type: Interventional

Funder types: Other

Identifiers

NCT01420874

2011-025

Details and patient eligibility

About

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.

Full description

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

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Minor changes from these guidelines will be allowed at the discretion of the attending team under special circumstances. The reasons for exceptions will be documented.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

FOLFOX6 & EGFRBi armed ATC Infusions

Experimental group

Description:

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) for continuous infusion of 5-FU. Adv. colorectal and pancreatic pts. w/no other standard chemo available, \& in pts who cannot receive FOLFOX chemo, immunotherapy may be given w/o antecedent chemo. 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 subsequent doses will be administered once weekly, for 3 weeks, then 12 weeks post aATC#1. Dose escalation level(per infusion): Level 0-5 billion; Level 1-10 billion; Level 2-20 billion; Level 3-40 billion

Treatment:

Drug: FOLFOX6

Biological: EGFRBi armed ATC Infusions