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

Primary Purpose

Colorectal Cancer

Status
Terminated
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Adoptive Cell Therapy (ACT)
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring MSI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Oslo University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adoptive Cell Therapy (ACT)

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
January 30, 2018
Last Updated
June 12, 2019
Sponsor
Oslo University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03431311
Brief Title
T Cell Receptor Based Therapy of Metastatic Colorectal Cancer
Acronym
TCR-CRC-001
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
March 8, 2018 (Actual)
Primary Completion Date
June 12, 2019 (Actual)
Study Completion Date
June 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
MSI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adoptive Cell Therapy (ACT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Adoptive Cell Therapy (ACT)
Intervention Description
T cell receptor based therapy of metastatic colorectal cancer with mRNA-engineered T cells targeting mutant transforming growth factor beta receptor type II (TGFβII)
Primary Outcome Measure Information:
Title
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
Description
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
PFS defined as time from treatment to objective progression (as assessed by RECIST v1.1)
Time Frame
2 years
Title
Radiological response rate (ORR)
Description
ORR defined as the proportion of patients with an objective tumor response
Time Frame
2 years
Title
Overall survival (OS)
Description
OS defined as time from treatment to date of death from any cause
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Svein Dueland, MD PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0379
Country
Norway

12. IPD Sharing Statement

Learn more about this trial

T Cell Receptor Based Therapy of Metastatic Colorectal Cancer

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