T Cell Receptor Based Therapy of Metastatic Colorectal Cancer

NCT ID: NCT03431311

Last Updated: 2019-06-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-08
• Study Completion Date: 2019-06-12

Brief Summary

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

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 2x109 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.

Group Type: EXPERIMENTAL

Adoptive Cell Therapy (ACT)

Intervention Type: BIOLOGICAL

T cell receptor based therapy of metastatic colorectal cancer with mRNA-engineered T cells targeting mutant transforming growth factor beta receptor type II (TGFβII)

Interventions

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)

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Svein Dueland

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Svein Dueland, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Oslo University Hospital

Oslo, , Norway

Countries

Norway

Other Identifiers

TCR-CRC-001

Identifier Type: -

Identifier Source: org_study_id