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

• Sponsor: Oslo University Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03431311
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 15.1
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Mar 8, 2018
• Actual Primary Completion Date: Jun 12, 2019
• Actual Study Completion Date: Jun 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 [2 years]

   Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0

Secondary Outcome Measures

1. Progression free survival (PFS) [2 years]

   PFS defined as time from treatment to objective progression (as assessed by RECIST v1.1)

2. Radiological response rate (ORR) [2 years]

   ORR defined as the proportion of patients with an objective tumor response

3. Overall survival (OS) [2 years]

   OS defined as time from treatment to date of death from any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Oslo University Hospital	Oslo		Norway	0379

Sponsors and Collaborators

• Oslo University Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Svein Dueland, Principal Investigator, Oslo University Hospital
• ClinicalTrials.gov Identifier: NCT03431311
• Other Study ID Numbers: TCR-CRC-001
• First Posted: Feb 13, 2018
• Last Update Posted: Jun 13, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Svein Dueland, Principal Investigator, Oslo University Hospital: MSI
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

No Results Posted as of Jun 13, 2019