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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Barbara Ann Karmanos Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Minsig Choi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01420874
First received: August 17, 2011
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

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. [ 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) ] [ Designated as safety issue: Yes ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Approximately every 8 weeks to until 1 year ] [ Designated as safety issue: No ]
    CT or PET Scan

  • Overall Survival [ Time Frame: Approximately every 8 weeks to until 1 year ] [ Designated as safety issue: No ]
    CT or PET Scan


Estimated Enrollment: 30
Study Start Date: August 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420874

Contacts
Contact: Minsig Choi, M.D. 313-576-8712 choim@karmanos.org

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48601
Sub-Investigator: Lawrence G. Lum, M.D., DSc         
Sub-Investigator: Anthony F. Shields, M.D., Ph.D.         
Sub-Investigator: Philip A. Philip, M.D., Ph.D.         
Sub-Investigator: Abi Deol, M.D.         
Sub-Investigator: Zaid Al-Kadhimi, M.D.         
Sub-Investigator: Archana Thakur, Ph.D.         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Minsig Choi, M.D. Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Minsig Choi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01420874     History of Changes
Other Study ID Numbers: 2011-025
Study First Received: August 17, 2011
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Neoplasms
Carcinoma
Colonic Neoplasms
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
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
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 26, 2014