CClinicalTrials.gg
TerminatedNCT03431311TCR-CRC-001Updated Jun 13, 2019

T Cell Receptor Based Therapy of Metastatic Colorectal Cancer

A Phase 1/2 interventional study of Adoptive Cell Therapy (ACT) in Colorectal Cancer, sponsored by Oslo University Hospital. Terminated at 1 site in Norway. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-06-13.

Sponsored by Oslo University Hospital · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Sponsor decision
Phase
Phase 1/2
Study type
Interventional
Enrollment
1
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Colorectal Cancer

Keywords

  • MSI
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
1 participant (actual)

Study arms

  • 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)

Interventions

  • BiologicalAdoptive 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)

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 2 years

Secondary outcomes

  1. Progression free survival (PFS)

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

    Time frame: 2 years

  2. Radiological response rate (ORR)

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

    Time frame: 2 years

  3. Overall survival (OS)

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

    Time frame: 2 years

06

Study locations

1 site
  • Oslo University Hospital
    Oslo, 0379, Norway
07

Registry details

Key details

Study ID
NCT03431311
Lead sponsor
Oslo University Hospital
Responsible party
Svein Dueland (Principal Investigator, Oslo University Hospital) — Principal investigator
First posted
Feb 13, 2018
Start date
Mar 8, 2018
Primary completion
Jun 12, 2019
Completion
Jun 12, 2019
Last update
Jun 13, 2019

Study contacts

Svein Dueland, MD PhD
principal investigator · Oslo University Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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