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

• ClinicalTrials.gov Identifier: NCT01420874
• Recruitment Status: Completed
• First Posted: August 22, 2011
• Last Update Posted: May 6, 2023
• Sponsor: Barbara Ann Karmanos Cancer Institute
• Information provided by (Responsible Party): Anthony F. Shields, MD PhD, Barbara Ann Karmanos Cancer Institute

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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	Phase 1

Detailed 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Advanced Colorectal or Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Armed Activated T-Cells (Phase Ib)
• Actual Study Start Date: August 17, 2011
• Actual Primary Completion Date: October 19, 2020
• Actual Study Completion Date: October 19, 2020

Arms and Interventions

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, 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

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) 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.; Other Names: leucovorin (FOLinic acid); Fluorouracil; OXaliplatin; 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 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

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 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) ]
   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.

Secondary Outcome Measures :

1. 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 [ Time Frame: 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) ]
   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.
2. Determining the tumor response rate [ Time Frame: Approximately every 8 weeks to until 1 year ]
   CT or PET Scan
3. Overall Survival [ Time Frame: Approximately every 8 weeks to until 1 year ]
   CT or PET Scan

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Michigan

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48601

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

Investigators

• Principal Investigator: Anthony Shields, M.D. PhD; Barbara Ann Karmanos Cancer Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Anthony F. Shields, MD PhD, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT01420874
• Other Study ID Numbers: 2011-025
• First Posted: August 22, 2011
• Last Update Posted: May 6, 2023
• Last Verified: May 2023

Additional relevant MeSH terms:

Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Leucovorin; Fluorouracil; Oxaliplatin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antidotes; Protective Agents; Vitamin B Complex; Vitamins