T Cell Receptor Based Therapy of Metastatic Colorectal Cancer (TCR-CRC-001)

• ClinicalTrials.gov Identifier: NCT03431311
• Recruitment Status: Terminated
• First Posted: February 13, 2018
• Last Update Posted: June 13, 2019
• Sponsor: Oslo University Hospital
• Information provided by (Responsible Party): Svein Dueland, Oslo University Hospital

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Biological: Adoptive Cell Therapy (ACT)	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 8, 2018
• Actual Primary Completion Date: June 12, 2019
• Actual Study Completion Date: June 12, 2019

Arms and Interventions

Arm	Intervention/treatment
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 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.	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)

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Norway

Oslo University Hospital

Oslo, Norway, 0379

Sponsors and Collaborators

Oslo University Hospital

Investigators

• Principal Investigator: Svein Dueland, MD PhD; Oslo University Hospital

More Information

• Responsible Party: Svein Dueland, Principal Investigator, Oslo University Hospital
• ClinicalTrials.gov Identifier: NCT03431311
• Other Study ID Numbers: TCR-CRC-001
• First Posted: February 13, 2018
• Last Update Posted: June 13, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Svein Dueland, Oslo University Hospital:

MSI

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases