T Cell Receptor Based Therapy of Metastatic Colorectal Cancer

Overview

T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)

Full Title of Study: “Protocol for Treatment Under Hospital Exemption: T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 12, 2019

Detailed Description

Patients with advanced metastatic colorectal cancer who have no other effective treatment options will be offered the treatment. These patients have a poor prognosis, and there is a strong need for improved therapy. The patients will be given adoptive cell therapy (ACT) with Radium-1 TCR+ T cells transiently redirected against the TGFβRII frameshift antigen which is expressed in MSI+ colon cancer. The first report on TCR therapy in colon cancer was targeting carcinoembryonic antigen (CEA) where some evidence of clinical response was seen, but the T-cell function may have been inhibited due to the necessity to resolve the severe colitis which occurred due to the presence of CEA in normal cells in the colon. This demonstrates the feasibility of T-cell therapy in metastatic colon cancer, but also the limitations of targeting CEA as an antigen.

Interventions

  • Biological: Adoptive Cell Therapy (ACT)
    • T cell receptor based therapy of metastatic colorectal cancer with mRNA-engineered T cells targeting mutant transforming growth factor beta receptor type II (TGFβII)

Arms, Groups and Cohorts

  • Experimental: Adoptive Cell Therapy (ACT)
    • The ACT will be administered as two intravenous (i.v.) injections of GMP TCR T cells per week for 6 weeks. Escalating dose per week, from 1 x108 cells (week 1) to 2×109 cells (week 4 onwards) using a central venous catheter. The doses listed indicate the maximum number of T cells per injection at any given time point.

Clinical Trial Outcome Measures

Primary Measures

  • Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
    • Time Frame: 2 years
    • Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0

Secondary Measures

  • Progression free survival (PFS)
    • Time Frame: 2 years
    • PFS defined as time from treatment to objective progression (as assessed by RECIST v1.1)
  • Radiological response rate (ORR)
    • Time Frame: 2 years
    • ORR defined as the proportion of patients with an objective tumor response
  • Overall survival (OS)
    • Time Frame: 2 years
    • OS defined as time from treatment to date of death from any cause

Participating in This Clinical Trial

Inclusion Criteria

  • Patients with metastatic colon cancer which is MSI+ with the presence of the -1A deletion in TGFβRII gene, and positive for HLA-A02 genotype – Measurable disease – Female or male patients. Fertile females must have a negative pregnancy test before inclusion in the trial. Both fertile men and women must be ready and able to use highly effective methods of contraception, defined as use of oral, implanted, injectable, and mechanical or barrier products for the prevention of pregnancy during participation of the trial – Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1 – Age 18 years and older – Life expectancy of at least 3 months – Signed informed consent (by the subject or subject's legal representative) obtained before any trial-related procedures. – Adequate organ function, measured by pre-defined laboratory values Exclusion criteria – Other metastatic malignancies – Any other anti-tumour treatment within 4 weeks prior to first administration of cells. – Steroid treatment, except substitution dose – Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina or serious cardiac arrhythmia – Active infection requiring antibiotic therapy – Pregnancy or lactation – Known hypersensitivity to any of the components of the investigational product – Patients who test positive for hepatitis B, C, HIV or syphilis – Any reason why, in the opinion of the investigator, the patient should not participate

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Oslo University Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Svein Dueland, Principal Investigator – Oslo University Hospital
  • Overall Official(s)
    • Svein Dueland, MD PhD, Principal Investigator, Oslo University Hospital

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.