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

Primary Purpose

Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

FOLFOX6

EGFRBi armed ATC Infusions

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFOX6 & EGFRBi armed ATC Infusions

Arm 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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Determining the tumor response rate

CT or PET Scan

Overall Survival

CT or PET Scan

Full Information

NCT ID

NCT01420874

First Posted

August 17, 2011

Last Updated

May 4, 2023

Sponsor

Barbara Ann Karmanos Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT01420874

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

August 17, 2011 (Actual)

Primary Completion Date

October 19, 2020 (Actual)

Study Completion Date

October 19, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FOLFOX6 & EGFRBi armed ATC Infusions

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

FOLFOX6

Other Intervention Name(s)

leucovorin (FOLinic acid), Fluorouracil, OXaliplatin

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

EGFRBi armed ATC Infusions

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Description

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)

Secondary Outcome Measure Information:

Title

Description

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)

Title

Determining the tumor response rate

Description

CT or PET Scan

Time Frame

Approximately every 8 weeks to until 1 year

Title

Overall Survival

Description

CT or PET Scan

Time Frame

Approximately every 8 weeks to until 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anthony Shields, M.D. PhD

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Barbara Ann Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48601

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

32939319

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.

Results Reference

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

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