Colorectal CarcinomaPhase 1ATACCNCT02577588
Trial of Adoptive T Cell Therapy With Activated P53 Specific T Cells for Treatment of Advanced Colorectal Cancer
A Phase 1 study testing re-activated T cells in people with Colorectal Carcinoma, run by National Center for Tumor Diseases, Heidelberg at 1 site in Germany.
Trial summary
The study "Phase I trial of Adoptive T cell Therapy with Activated P53 specific T cells for Treatment of Advanced Colorectal Cancer" is an open label, single arm trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Carcinoma
- What is being tested?
- re-activated T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteGermany
- Study dates
- 1 May 2016to 19 Feb 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed UICC stage IV colorectal cancer and non resectable primary tumor and/or metastases
- Previous palliative standard systemic treatment with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab, and currently under respective treatment
- The following situation after at least four cycles with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab should apply:
- Disease control (stable disease, partial response or complete response) according routine imaging
- Resection of tumor and/or metastases still impossible
- Tolerability of systemic treatment
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- The decision of the treating physician is to continue the standard background treatment
- Presence of tumor-reactive T cells in the blood as detected by ex vivo IFN-γ EliSpot assay and classification of the reaction as a response in a blood sample
- ECOG-performance status 0 or 1
- Adequate vein status at both cubital fossas for 16 G puncture (white permanent venous catheter, Braunüle; EN ISO 6009)
- Age ≥ 18 years, any ethnic origin and gender
- Ability of the patient to understand the character and individual consequences of the clinical trial
- Patients should be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Written informed consent (must be available before enrolment in the trial)
- Negative pregnancy test (females of childbearing potential)
- Women with childbearing potential and male patients with partners of childbearing potential should be willing to use adequate contraception (failure rate less than 1% per year when used consistently and correctly) during the study and three month last application of T cell therapy
- At the screening visit the following laboratory parameters apply and should be within the ranges specified:
- Lab Parameter Range WBC ≥4000/mm3 (≥4000/ul) Platelets ≥80.000/mm3 (≥80.000/ul) Creatinine ≤1.5mg/dl ALT, AST, and total bilirubin < 2.5 x ULN HB > 9 g/dl
- HB is controlled again at day -11 at DRK Mannheim as part of the procedures before leukapheris.
Who cannot join
- Brain or leptomeningeal metastases, shown by MRI Scan during Screening phase or by routinely available other appropriate diagnostic (CT, MRI, PET) conducted within 3 months prior to inclusion.
- Previous malignancy within the past 5 years. However: Patients who had curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer treated by endoscopic resection and/or in situ carcinoma of the cervix are allowed for enrolment.
- History of organ allograft or prior hematopoetic stem cell transplantation
- History of inflammatory bowel disease (ulcerative colitis, Crohn's disease)
- History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis])
- History of motor neuropathy considered of autoimmune origin (e.g., Guillain-Barré Syndrome)
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- Clinically significant cardiac disease (NYHA Class III or IV).
- Other serious illnesses, which renders the patient unsuitable for study entry or multiple blood sampling
- Serious intercurrent illness, requiring hospitalization
- HIV and/or HBC/HCV positivity, tested by appropriate infection diagnostics during screening period
- Any active infection or signs or symptoms of infection
- Patient pregnant or breastfeeding
- History of hypersensitivity to the investigational medicinal product or to any excipient present in the investigational medicinal product or to anti-coagulance auxiliary medicianal product (Heparin prophylaxis)
- Treatment with immunosuppressive drugs (e.g. systemic corticosteroids) besides intermittent, anti-emetic steroid application during treatment with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab. Topical or inhalation steroids are permitted.
- Treatment with any approved anti-cancer therapy within 28 days prior to enrolment, except the background treatment FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab.as recommended by that trial protocol
- Treatment with any live attenuated vaccine within 4 weeks before first administration of investigational medicinal product
- Treatment with any other investigational agent or participation in another interventional clinical trial within 28 days prior to enrolment.
- No patient will be allowed to enroll in this trial more than once.
Trial locations and contacts
1 site in 1 country.
Germany1 site
National Center for Tumor desease NCT
Heidelberg, Baden-Wurttemberg, 69120
About this study
Official title: Phase I Trial of Adoptive T Cell Therapy With Activated P53 Specific T Cells for Treatment of Advanced Colorectal Cancer
The study "Phase I trial of Adoptive T cell Therapy with Activated P53 specific T cells for Treatment of Advanced Colorectal Cancer" is an open label, single arm trial.
Read the detailed description
Most patients with colorectal carcinoma (CRC) accumulate high numbers of endogenous tumor antigen specific cytotoxic and helper memory T cells in their blood. Upon appropriate reactivation, tumor antigen specific T cells can recognize and eliminate autologous tumor cells. This can be achieved ex vivo by their stimulation with antigen pulsed autologous dendritic cells in the absence of regulatory T cells. Upon adoptive transfer, specifically reactivated T cells from cancer patients can efficiently reject autologous human tumors in vivo.
A major target antigen of anti tumor effector T cells in CRC patients is p53, which is overexpressed in many colorectal cancers. Within this clinical trial, high numbers of endogenous tumor specific T cells will be harvested by leukapheresis from the blood of CRC patients harbouring p53-reactive T cells. Isolated T cells will be depleted from regulatory T cells and specifically reactivated for three days ex vivo with three synthetic long peptides containing the most immunogenic regions of p53 using autologous dendritic cells as antigen presenting cells. Activated T cells will be re-infused into the patients.
Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10^7 (first three or six patients) or 5x10^8 (last four or seven patients) cells.
Patient treatment and follow-up will be performed at the National Center for Tumor Diseases (NCT) and at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg. Leukapheresis will take place at the DRK-Blutspendedienst Baden-Württemberg-Hessen in Mannheim and generation of therapeutic cells will be performed at the GMP Unit Cellular Therapy of the DKFZ. Analysis of blood samples with respect to special immune parameters is carried out at the Immune Monitoring Laboratory, Department of Translational Immunology at the NCT, Heidelberg.
The primary objective of this study is to evaluate the safety and tolerability of an adoptive transfer of ex vivo reactivated p53 specific T cells obtained from peripheral blood.
- Conditions
- Colorectal Carcinoma
- Being tested
- re-activated T cells
- Keywords
- p53 Antigen, T cell therapy, autologous, Adoptive Cellular Immunotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
re-activated T cellsBiological
Also called autologous T cells, p53 activated T cells
autologous reactivated T cells against p53
| Study group | Role | What they receive |
|---|---|---|
| re-activated T cells | Experimental | Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10^7 (first three or six patients) or 5x10^8 (last four or seven patients) cells. Receives: Biological: re-activated T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
The primary endpoint is the Dose Limiting Toxicity (DLT), defined as: any adverse event (AE) ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03), that is judged by the investigator as definitely, probably or possibly related to the investigational medicinal product (IMP) or to the combination of the IMP and the treatment with FOLFOX 6/Bevacizumab.
Measured: 45 days
Secondary outcomes (1)
evaluation of p53 specific T cell Responses by analysing data from EliSpot assay
The response of a patient to the p53 peptide mix or to each of the single p53 peptides
Measured: day 0, 10, 17, 24, 31
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2015 (estimated)
- Study start1 May 2016
- Primary completion19 Feb 2018
- Study completion19 Feb 2018
Why it stopped: not feasible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center for Tumor Diseases, Heidelberg
- Sponsor type
- University, hospital or other
- Collaborators
- German Cancer Research Center, University Hospital Heidelberg
- Responsible party
- Sponsor
- Investigators
- Alexis Ulrich, MD Prof. Dr., Principal investigator, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02577588
- Sponsor's protocol ID
- NCT-2009-11-03-1055
- Acronym
- ATACC
- Status last verified
- Mar 2018
- First submitted
- 6 May 2015
- Last updated
- 11 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Adoptive T Cell Therapy With Activated P53 Specific T Cells for Treatment of Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02577588
- Acronym / sponsor ID
- ATACC / NCT-2009-11-03-1055
- Conditions
- Colorectal Carcinoma
- Keywords
- p53 Antigen, T cell therapy, autologous, Adoptive Cellular Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: not feasible
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Center for Tumor Diseases, HeidelbergUniversity, hospital or other
- Collaborators
- German Cancer Research Center, University Hospital Heidelberg
- Study start
- 1 May 2016 (actual)
- Primary completion
- 19 Feb 2018 (actual)
- Study completion
- 19 Feb 2018 (actual)
- First posted
- 16 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study "Phase I trial of Adoptive T cell Therapy with Activated P53 specific T cells for Treatment of Advanced Colorectal Cancer" is an open label, single arm trial.
Detailed description
Most patients with colorectal carcinoma (CRC) accumulate high numbers of endogenous tumor antigen specific cytotoxic and helper memory T cells in their blood. Upon appropriate reactivation, tumor antigen specific T cells can recognize and eliminate autologous tumor cells. This can be achieved ex vivo by their stimulation with antigen pulsed autologous dendritic cells in the absence of regulatory T cells. Upon adoptive transfer, specifically reactivated T cells from cancer patients can efficiently reject autologous human tumors in vivo.
A major target antigen of anti tumor effector T cells in CRC patients is p53, which is overexpressed in many colorectal cancers. Within this clinical trial, high numbers of endogenous tumor specific T cells will be harvested by leukapheresis from the blood of CRC patients harbouring p53-reactive T cells. Isolated T cells will be depleted from regulatory T cells and specifically reactivated for three days ex vivo with three synthetic long peptides containing the most immunogenic regions of p53 using autologous dendritic cells as antigen presenting cells. Activated T cells will be re-infused into the patients.
Ten patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10^7 (first three or six patients) or 5x10^8 (last four or seven patients) cells.
Patient treatment and follow-up will be performed at the National Center for Tumor Diseases (NCT) and at the Department of General, Visceral and Transplantation Surgery, University of Heidelberg. Leukapheresis will take place at the DRK-Blutspendedienst Baden-Württemberg-Hessen in Mannheim and generation of therapeutic cells will be performed at the GMP Unit Cellular Therapy of the DKFZ. Analysis of blood samples with respect to special immune parameters is carried out at the Immune Monitoring Laboratory, Department of Translational Immunology at the NCT, Heidelberg.
The primary objective of this study is to evaluate the safety and tolerability of an adoptive transfer of ex vivo reactivated p53 specific T cells obtained from peripheral blood.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| re-activated T cells | Experimental | Biological: re-activated T cellsTen patients with CRC stage UICC IV under routine first line FOLFOX 6/Bevacizumab therapy are planned to receive a singular treatment with an autologous T cell product at a dose of 5x10^7 (first three or six patients) or 5x10^8 (last four or seven patients) cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically confirmed UICC stage IV colorectal cancer and non resectable primary tumor and/or metastases
- Previous palliative standard systemic treatment with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab, and currently under respective treatment
- The following situation after at least four cycles with FOLFOX, FOLFIRI, or FOLFIRINOX in combination with Bevacizumab or Cetuximab/Panitumumab should apply:
- Presence of tumor-reactive T cells in the blood as detected by ex vivo IFN-γ EliSpot assay and classification of the reaction as a response in a blood sample
- ECOG-performance status 0 or 1
Key exclusion criteria (18 listed)
- Brain or leptomeningeal metastases, shown by MRI Scan during Screening phase or by routinely available other appropriate diagnostic (CT, MRI, PET) conducted within 3 months prior to inclusion.
- Previous malignancy within the past 5 years. However: Patients who had curatively treated basal cell carcinoma of the skin, early gastrointestinal cancer treated by endoscopic resection and/or in situ carcinoma of the cervix are allowed for enrolment.
- History of organ allograft or prior hematopoetic stem cell transplantation
- History of inflammatory bowel disease (ulcerative colitis, Crohn's disease)
- History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| re-activated T cellsAlso: autologous T cells, p53 activated T cellsautologous reactivated T cells against p53 | Biological | re-activated T cells |
Primary outcome
Safety
Time frame: 45 days
The primary endpoint is the Dose Limiting Toxicity (DLT), defined as: any adverse event (AE) ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.03), that is judged by the investigator as definitely, probably or possibly related to the investigational medicinal product (IMP) or to the combination of the IMP and the treatment with FOLFOX 6/Bevacizumab.
1 secondary outcome
evaluation of p53 specific T cell Responses by analysing data from EliSpot assay
Time frame: day 0, 10, 17, 24, 31
Results and safety
The study was stopped early (reason given: not feasible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexis Ulrich, MD Prof. Dr. principal investigator
University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing re-activated T cells in people with Colorectal Carcinoma, run by National Center for Tumor Diseases, Heidelberg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: not feasible). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: 45 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2018.