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

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)

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

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: Adoptive Cell Therapy (ACT)

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0379
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2018
• Primary Completion (Actual): June 12, 2019
• Study Completion (Actual): June 12, 2019

Study Registration Dates

• First Submitted: January 30, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: MSI
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: TCR-CRC-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No