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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03431311
Recruitment Status : Terminated (Sponsor decision)
First Posted : February 13, 2018
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
Svein Dueland, Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE January 30, 2018
First Posted Date  ICMJE February 13, 2018
Last Update Posted Date June 13, 2019
Actual Study Start Date  ICMJE March 8, 2018
Actual Primary Completion Date June 12, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03431311 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
  • Progression free survival (PFS) [ Time Frame: 2 years ]
    PFS defined as time from treatment to objective progression (as assessed by RECIST v1.1)
  • Radiological response rate (ORR) [ Time Frame: 2 years ]
    ORR defined as the proportion of patients with an objective tumor response
  • Overall survival (OS) [ Time Frame: 2 years ]
    OS defined as time from treatment to date of death from any cause
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE T Cell Receptor Based Therapy of Metastatic Colorectal Cancer
Official Title  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE 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)
Study Arms  ICMJE 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.

Intervention: Biological: Adoptive Cell Therapy (ACT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 12, 2019)
1
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2018)
5
Actual Study Completion Date  ICMJE June 12, 2019
Actual Primary Completion Date June 12, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03431311
Other Study ID Numbers  ICMJE TCR-CRC-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Svein Dueland, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Svein Dueland, MD PhD Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP