Clinical trial NCT01420874: Anti-CD3 x Anti-Erbitux® Armed Activated T Cells (Phase Ib) for Gastrointestinal (GI Cancer)
Official title: Treatment of Advanced Colorectal or Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Armed Activated T-Cells (Phase Ib)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Cancer of Pancreas
Pancreatic Neoplasm
Malignant Neoplasm of Large Intestine
Malignant Tumor of Colon
Colon Carcinoma
Cancer of Colon
Pancreatic Cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
First posted: 2011-08-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 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 outcomes:
measure: 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
timeFrame: 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)
measure: Determining the tumor response rate
timeFrame: Approximately every 8 weeks to until 1 year
measure: Overall Survival
timeFrame: Approximately every 8 weeks to until 1 year
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Anthony Shields, M.D. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.