Colorectal CancerPhase 1/2STARTREKNCT00986518
T Regulatory Lymphocytes (Treg) Depletion for Cancer Treatment Efficacy and Safety Study
A Phase 1/2 study testing Adaptive autologous cell immunotherapy in people with Colorectal Cancer, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of an efficacious immune response needed to cure cancer. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Adaptive autologous cell immunotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2012to Feb 2013
- Phase
- Phase 1/2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Colon or rectal adenocarcinoma histologically proven;
- Hepatic or lung metastasis (at least one with size >1cm on CT-scan);
- Not eligible for surgery;
- Prior treatment with fluoropyrimidines, CPT11, oxaliplatine and EGFR antibodies (Cetuximab ou Panitumumab) ± bevacizumab; When tumor has a mutated Kras, prior treatment with EGFR antibodies is not mandatory;
- No local recurrence (on CT-scan, sonogram and/or colonoscopy);
- Karnofsky index > 70 and PS 0 or 1;
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- ASA Score < 3 ;
- Absence of chronic hepatopathy ;
- Lab test : WBC: neutrophil> 2.0 109 / l, lymphocytes > 1.5 109 / l; creatinine < 1.5 x ULN or clearance ≥ 60 ml/min; AST et ALT< 5 x ULN, alkaline phosphatases < 3 x ULN; LDH < 3 x ULN; negative Coombs test ;
- Signed informed consent.
Who cannot join
- Peritoneal carcinosis on CT-scan, MRI or PET-scan;
- Contra-indication to MRI;
- Patient with known allergy to iodinated contrast agent, gadolinium or Sulfate Hexafluoron ;
- Presence of metastasis at sites other than lung and liver;
- Documented history of auto-immune disease and/ or progressing disease;
- Infection at whatever site;
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- Documented history of allo- or autograft;
- Undernutrition, BMI < 18;
- History of other cancer < 5 years (excluding cancer in situ of the cervix and baso-cellular tumor of the skin) or progressing disease;
- Women of child bearing age without contraception , or pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
France1 site
Service hépato-gastro-enterologie, Pitié-Salpêtrière Hospital
Paris, 75013
About this study
Official title: Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of an efficacious immune response needed to cure cancer. To treat advanced metastatic colorectal cancer, the investigators propose an immunotherapy consisting in autologous lymphocytes infusion depleted from T-regulatory cells, associated with a 5-day prior lymphoid-ablative chemotherapy associating cyclophosphamide (day 1 \& 2) with fludarabine (day 1 to 5). To administer treatment and monitor chemotherapy safety, patients will be hospitalized for 3 weeks until complete recovery from chemotherapy. Patients will then be followed-up ambulatory for 9 months during which time they will be assessed for tumor size with computed tomography (CT) - scan (primary criteria).
Read the detailed description
The primary goal of the proposed clinical trial is to eliminate cancer tumor using an autologous cell therapy aiming at mounting an efficient immune anti-tumor response by selectively depleting regulatory T-cell during a controlled amount of time. This strategy will be tested in patients with hepatic metastases from colorectal who are not eligible for surgery.
This is an open-label single cohort phase I-II therapeutic trial. Patients with hepatic metastases from primary colorectal cancer, not eligible to surgery and relapsing from conventional chemotherapy and/or targeted therapy, will be included.
Following patient inclusion:
- A lymphapheresis will be performed at D-15 which will be subjected to cell sorting /purification of regulatory T cells on the one hand and T lymphocytes depleted from regulatory T cells (effectors T-cells) on the other, and subsequently frozen and stored (The procedures for ex vivo regulatory T cell depletion has been validated in a previous study - AFSSAPS- TC 192) ;
- A lymphoid-ablative chemotherapy (cyclophosphamide + fludarabine) will be perform from D1 to D5,
- Autologous effector T-cells administration will be performed at D7. Efficacy will be assessed through tumor size change. Change in tumor size will be assessed with CTscans (RECIST criteria), MRIs (functional criteria following injection: DCEMRI and diffusion MRI to assess change in cellularity and tumor necrosis and morphological criteria RECIST), and sonography with contrast injection (to assess vascular microcirculation). Assessments will be done prior to lymphoid-ablation and then monthly for 9 months. Safety will be systematically assessed daily during in-patient period using the World Health Organisation - Common Toxicity Criteria (WHO-CTC).
- Conditions
- Colorectal Cancer
- Being tested
- Adaptive autologous cell immunotherapy
- Keywords
- Advanced Colorectal Cancer, Hepatic and/or lung metastasis, Adaptive autologous cell immunotherapy, T- regulatory lymphocyte depletion, Neo-adjuvant reduced intensity chemotherapeutic conditioning
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adaptive autologous cell immunotherapyBiological
each patient will undergo a blood cytapheresis to collect circulating lymphocytes. Ex-vivo cell sorting procedure will deplete patient's collected lymphocytes from regulatory T cells. Autologous Treg-depleted lymphocytes will be administered to the patient following a 5-day reduced intensity chemo-therapeutic conditioning.
| Study group | Role | What they receive |
|---|---|---|
| adaptive cell immunotherapy | Experimental | Not described Receives: Biological: Adaptive autologous cell immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria)
Measured: from Month 1 to Month 9
Secondary outcomes (5)
MRI : Assessment of tumor necrosis, cellularity and morphological criteria RECIST 1.1 (functional criteria following injection : DCEMRI and diffusion MRI)
Measured: Month 1 to Month 9
Sonography : assessment of vascular micro-circulation with contrast injection,
Measured: Month 1 to Month 9
Immune cell reconstitution will be assessed through measuring rate of regulatory T-cell reconstitution,
Measured: day 7 to 28
Clinical Exam (WHO-CTC), Vital Signs, Adverse events
Measured: day 1 to 28
Laboratory test: hepatic function, immune function, haematology
Measured: day 1 to 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2009 (estimated)
- Study startOct 2012
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Klatzmann, MD, PhD, Principal investigator, Pitié-Salpêtrière Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00986518
- Sponsor's protocol ID
- P080601
- Acronym
- STARTREK
- Status last verified
- Sep 2013
- First submitted
- 29 Sep 2009
- Last updated
- 25 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study
- ClinicalTrials.gov ID
- NCT00986518
- Acronym / sponsor ID
- STARTREK / P080601
- Conditions
- Colorectal Cancer
- Keywords
- Advanced Colorectal Cancer, Hepatic and/or lung metastasis, Adaptive autologous cell immunotherapy, T- regulatory lymphocyte depletion, Neo-adjuvant reduced intensity chemotherapeutic conditioning
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 30 Sep 2009 (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.
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of an efficacious immune response needed to cure cancer. To treat advanced metastatic colorectal cancer, the investigators propose an immunotherapy consisting in autologous lymphocytes infusion depleted from T-regulatory cells, associated with a 5-day prior lymphoid-ablative chemotherapy associating cyclophosphamide (day 1 \& 2) with fludarabine (day 1 to 5). To administer treatment and monitor chemotherapy safety, patients will be hospitalized for 3 weeks until complete recovery from chemotherapy. Patients will then be followed-up ambulatory for 9 months during which time they will be assessed for tumor size with computed tomography (CT) - scan (primary criteria).
Detailed description
The primary goal of the proposed clinical trial is to eliminate cancer tumor using an autologous cell therapy aiming at mounting an efficient immune anti-tumor response by selectively depleting regulatory T-cell during a controlled amount of time. This strategy will be tested in patients with hepatic metastases from colorectal who are not eligible for surgery.
This is an open-label single cohort phase I-II therapeutic trial. Patients with hepatic metastases from primary colorectal cancer, not eligible to surgery and relapsing from conventional chemotherapy and/or targeted therapy, will be included.
Following patient inclusion:
- A lymphapheresis will be performed at D-15 which will be subjected to cell sorting /purification of regulatory T cells on the one hand and T lymphocytes depleted from regulatory T cells (effectors T-cells) on the other, and subsequently frozen and stored (The procedures for ex vivo regulatory T cell depletion has been validated in a previous study - AFSSAPS- TC 192) ;
- A lymphoid-ablative chemotherapy (cyclophosphamide + fludarabine) will be perform from D1 to D5,
- Autologous effector T-cells administration will be performed at D7. Efficacy will be assessed through tumor size change. Change in tumor size will be assessed with CTscans (RECIST criteria), MRIs (functional criteria following injection: DCEMRI and diffusion MRI to assess change in cellularity and tumor necrosis and morphological criteria RECIST), and sonography with contrast injection (to assess vascular microcirculation). Assessments will be done prior to lymphoid-ablation and then monthly for 9 months. Safety will be systematically assessed daily during in-patient period using the World Health Organisation - Common Toxicity Criteria (WHO-CTC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| adaptive cell immunotherapy | Experimental | Biological: Adaptive autologous cell immunotherapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Colon or rectal adenocarcinoma histologically proven;
- Hepatic or lung metastasis (at least one with size >1cm on CT-scan);
- Not eligible for surgery;
- Prior treatment with fluoropyrimidines, CPT11, oxaliplatine and EGFR antibodies (Cetuximab ou Panitumumab) ± bevacizumab; When tumor has a mutated Kras, prior treatment with EGFR antibodies is not mandatory;
- No local recurrence (on CT-scan, sonogram and/or colonoscopy);
Key exclusion criteria (10 listed)
- Peritoneal carcinosis on CT-scan, MRI or PET-scan;
- Contra-indication to MRI;
- Patient with known allergy to iodinated contrast agent, gadolinium or Sulfate Hexafluoron ;
- Presence of metastasis at sites other than lung and liver;
- Documented history of auto-immune disease and/ or progressing disease;
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 |
|---|---|---|
| Adaptive autologous cell immunotherapyeach patient will undergo a blood cytapheresis to collect circulating lymphocytes. Ex-vivo cell sorting procedure will deplete patient's collected lymphocytes from regulatory T cells. Autologous Treg-depleted lymphocytes will be administered to the patient following a 5-day reduced intensity chemo-therapeutic conditioning. | Biological | adaptive cell immunotherapy |
Primary outcome
Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria)
Time frame: from Month 1 to Month 9
5 secondary outcomes
MRI : Assessment of tumor necrosis, cellularity and morphological criteria RECIST 1.1 (functional criteria following injection : DCEMRI and diffusion MRI)
Time frame: Month 1 to Month 9
Sonography : assessment of vascular micro-circulation with contrast injection,
Time frame: Month 1 to Month 9
Immune cell reconstitution will be assessed through measuring rate of regulatory T-cell reconstitution,
Time frame: day 7 to 28
Clinical Exam (WHO-CTC), Vital Signs, Adverse events
Time frame: day 1 to 28
Laboratory test: hepatic function, immune function, haematology
Time frame: day 1 to 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2013.
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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.
David Klatzmann, MD, PhD principal investigator
Pitié-Salpêtrière Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Adaptive autologous cell immunotherapy in people with Colorectal Cancer, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 inclusion and 10 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: finished, as of the sponsor's last update on 25 Nov 2013. 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 France. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Tumor size of hepatic and/or lung metastases, as measured with tomodensitometry (RECIST 1.1 criteria) (time frame: from Month 1 to Month 9). 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 25 Nov 2013.