Gastrointestinal Metastatic CancerPhase 1NK-EGFR01NCT02845999
Allogenic Immunotherapy Based on Natural Killer (NK) Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab
A Phase 1 study testing allogenic immunotherapy based on Natural Killer cells adoptive transfer, cetuximab and Cyclophosphamide in people with Gastrointestinal Metastatic Cancer, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial summary
Gastrointestinal (GI) cancers account for the most common cancers. Despite recent advances in GI cancer treatments, the 5-year overall survival rate for these patients remain unacceptable, except for patients who are candidates for metastasis surgical resection. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Gastrointestinal Metastatic Cancer
- What is being tested?
- allogenic immunotherapy based on Natural Killer cells adoptive transfer, cetuximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2009to Jan 2013
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- metastatic gastrointestinal cancer (colorectal, pancreas, small intestine, bile ducts), gastrointestinal stromal tumor or digestive neuroendocrine tumor.
- presence of liver metastases
- Age > 18 and < 65 (male and female)
- ECOG performances status 0 or 1
- EGFR expression confirmed by immunohistochemistry
- allogenic donor with one or more KIR/MHC class I mismatch
Show all 9Show fewer
- absence of alternative treatment available
- evidence of progressive disease
- written informed consent
Who cannot join
- malignant secondary disease dated backed < 2 years (exception : in situ carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- hypersensitivity against one of the treatment of this study
- history of cardiac or respiratory failure
- history of auto-immune disease
- renal or hepatic failure
- pregnancy or lactation
Show all 10Show fewer
- patient with any medical or psychiatric condition or disease which would makes the patient inappropriate for entry into this study.
- EBV serology negative in recipient and positive in donor
- bilirubin greater than 1,5 times upper limit of normal
- ASAT and/or alkaline phosphatase greater than 5 times upper limit of normal in presence of liver metastases.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Allogenic Immunotherapy Based on Natural Killer Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab : a Phase I Trial
Gastrointestinal (GI) cancers account for the most common cancers. Despite recent advances in GI cancer treatments, the 5-year overall survival rate for these patients remain unacceptable, except for patients who are candidates for metastasis surgical resection. Strategies leading to a decrease of metastatic number and size will contribute to improve the probability to undergo a curative surgical procedure.
Haploidentical Natural Killer (NK) cells can persist and expand in vivo following adoptive transfer and may have a role in the treatment of selected malignancies, since the failure to recognize the appropriate KIR ligand on a mismatched tumor cell can trigger NK cell elimination of that target cell. NK also express an activating Fc receptor that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab, an IgG1 chimeric monoclonal antibody against colorectal cancers that expressed EGFR (epidermal growth factor receptor), improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed.
In an attempt to improve the outcome in GI cancers, we will conduct a phase I/II clinical trial assessing NK cell based immunotherapy. Patients with liver metastases related to a EGFR+ GI cancer, previously treated by a standard chemotherapy that did not achieve a complete response or a curative resection of residual metastases will be included in this phase I/II trial supported by the French National Institute of Cancer (INCA, PHRC 2005). This phase I/II study will involve 22 patients. The main objective of this study will be to demonstrate the safety of NK hepatic intraarterial infusion in association with cetuximab. Secondary objectives will include the assessment of the clinical efficacity of this strategy.
Read the detailed description
Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). Then 10 more patients will receive the recommended NK cell dose.
Dose escalation protocol : 3.10^6 ; 8.10^6 and 12.10^6 cells/kg of recipient body weight.
- Conditions
- Gastrointestinal Metastatic Cancer
- Being tested
- allogenic immunotherapy based on Natural Killer cells adoptive transfer, cetuximab, Cyclophosphamide, fludarabine, interleukin-2
- Keywords
- natural killer cells, adoptive transfer, allogenic immunotherapy, gastrointestinal cancer EGFR+
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allogenic immunotherapy based on Natural Killer cells adoptive transferBiological
day -1 : donor NK cell purification ; day 0 : adoptive transfer (according to a dose escalation) ; Dose escalation protocol : 3.10^6 ; 8.10^6 and 12.10^6 cells/kg of recipient body weight
cetuximabBiological
day -8 : cetuximab 400 mg/m2 ; day -1 and every week (for 7 weeks) : cetuximab 250 mg/m2
CyclophosphamideDrug
day -6 : cyclophosphamide 60 mg/Kg
fludarabineDrug
day -6 to day -2 : fludarabine 25 mg/m2
interleukin-2Drug
day -1 : addition of 1000 UI/ml of interleukin 2 to NK cells and overnight culture at 37°C, 5%CO2 ; day 0, hour +12 : 10 MUI of interleukin 2 injection, 2 times a week during 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Allogenic NK cells transfer | Experimental | Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). T Receives: Biological: allogenic immunotherapy based on Natural Killer cells adoptive transfer; Biological: cetuximab; Drug: Cyclophosphamide; Drug: fludarabine; Drug: interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients with clinical or biological grade 3 or 4 treatment-related adverse events as assessed by CTCAE v4.0
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study startNov 2009
- Primary completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Metastatic CancerStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02845999
- Sponsor's protocol ID
- N2005/48-A
- Acronym
- NK-EGFR01
- Status last verified
- Mar 2016
- First submitted
- 1 Dec 2011
- Last updated
- 27 Jul 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogenic Immunotherapy Based on Natural Killer Cell Adoptive Transfer in Metastatic Gastrointestinal Carcinoma Treated With Cetuximab : a Phase I Trial
- ClinicalTrials.gov ID
- NCT02845999
- Acronym / sponsor ID
- NK-EGFR01 / N2005/48-A
- Conditions
- Gastrointestinal Metastatic Cancer
- Keywords
- natural killer cells, adoptive transfer, allogenic immunotherapy, gastrointestinal cancer EGFR+
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Collaborators
- National Cancer Institute, France
- Study start
- Nov 2009
- Primary completion
- Jan 2013 (actual)
- First posted
- 27 Jul 2016 (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.
Gastrointestinal (GI) cancers account for the most common cancers. Despite recent advances in GI cancer treatments, the 5-year overall survival rate for these patients remain unacceptable, except for patients who are candidates for metastasis surgical resection. Strategies leading to a decrease of metastatic number and size will contribute to improve the probability to undergo a curative surgical procedure.
Haploidentical Natural Killer (NK) cells can persist and expand in vivo following adoptive transfer and may have a role in the treatment of selected malignancies, since the failure to recognize the appropriate KIR ligand on a mismatched tumor cell can trigger NK cell elimination of that target cell. NK also express an activating Fc receptor that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab, an IgG1 chimeric monoclonal antibody against colorectal cancers that expressed EGFR (epidermal growth factor receptor), improves overall survival and progression-free survival and preserves quality-of-life measures in patients with colorectal cancer in whom other treatments have failed.
In an attempt to improve the outcome in GI cancers, we will conduct a phase I/II clinical trial assessing NK cell based immunotherapy. Patients with liver metastases related to a EGFR+ GI cancer, previously treated by a standard chemotherapy that did not achieve a complete response or a curative resection of residual metastases will be included in this phase I/II trial supported by the French National Institute of Cancer (INCA, PHRC 2005). This phase I/II study will involve 22 patients. The main objective of this study will be to demonstrate the safety of NK hepatic intraarterial infusion in association with cetuximab. Secondary objectives will include the assessment of the clinical efficacity of this strategy.
Detailed description
Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). Then 10 more patients will receive the recommended NK cell dose.
Dose escalation protocol : 3.10^6 ; 8.10^6 and 12.10^6 cells/kg of recipient body weight.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogenic NK cells transfer | Experimental | Biological: allogenic immunotherapy based on Natural Killer cells adoptive transfer, Biological: cetuximab, Drug: Cyclophosphamide, Drug: fludarabine, Drug: interleukin-2Patients will be treated with a conditioning chemotherapy including 60 mg/kg intravenous cyclophosphamide, 25 mg/m2 intravenous fludarabine for 5 consecutive days and cetuximab. A lymphapheresis from an haploidentical related donor will be performed and T cells will be depleted . Allogenic NK cells will then be adoptively transferred by hepatic intraarterial infusion according to a dose escalation protocol (three doses with at least three patients per cohort)to define the dose-limiting toxicity (DLT). T |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- metastatic gastrointestinal cancer (colorectal, pancreas, small intestine, bile ducts), gastrointestinal stromal tumor or digestive neuroendocrine tumor.
- presence of liver metastases
- Age > 18 and < 65 (male and female)
- ECOG performances status 0 or 1
- EGFR expression confirmed by immunohistochemistry
Key exclusion criteria (10 listed)
- malignant secondary disease dated backed < 2 years (exception : in situ carcinoma of the cervix uteri, adequately treated skin basal cell carcinoma)
- hypersensitivity against one of the treatment of this study
- history of cardiac or respiratory failure
- history of auto-immune disease
- renal or hepatic failure
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 |
|---|---|---|
| allogenic immunotherapy based on Natural Killer cells adoptive transferday -1 : donor NK cell purification ; day 0 : adoptive transfer (according to a dose escalation) ; Dose escalation protocol : 3.10^6 ; 8.10^6 and 12.10^6 cells/kg of recipient body weight | Biological | Allogenic NK cells transfer |
| cetuximabday -8 : cetuximab 400 mg/m2 ; day -1 and every week (for 7 weeks) : cetuximab 250 mg/m2 | Biological | Allogenic NK cells transfer |
| Cyclophosphamideday -6 : cyclophosphamide 60 mg/Kg | Drug | Allogenic NK cells transfer |
| fludarabineday -6 to day -2 : fludarabine 25 mg/m2 | Drug | Allogenic NK cells transfer |
| interleukin-2day -1 : addition of 1000 UI/ml of interleukin 2 to NK cells and overnight culture at 37°C, 5%CO2 ; day 0, hour +12 : 10 MUI of interleukin 2 injection, 2 times a week during 3 weeks. | Drug | Allogenic NK cells transfer |
Primary outcome
number of patients with clinical or biological grade 3 or 4 treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 6 weeks
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 27 Jul 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 allogenic immunotherapy based on Natural Killer cells adoptive transfer, cetuximab and Cyclophosphamide in people with Gastrointestinal Metastatic Cancer, run by Centre Hospitalier Universitaire de Besancon 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 9 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 27 Jul 2016. 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 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 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?
number of patients with clinical or biological grade 3 or 4 treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 6 weeks). 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 27 Jul 2016.