Metastatic Colorectal CancerPhase 2IRAFUNCT02090101
Study Evaluating the Influence of LV5FU2 Bevacizumab Plus Anakinra Association on Metastatic Colorectal Cancer
A Phase 2 study testing ANAKINRA in people with Metastatic Colorectal Cancer, run by Centre Georges Francois Leclerc at 1 site in France.
Trial summary
The metastatic colon cancer is a major public health problem despite advances in chemotherapy; few new drugs are in development for the treatment of this pathology. Many studies have shown that human colon cancer is a tumor that is recognized by the immune system and the presence of lymphocytic infiltrates in the… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- ANAKINRA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteFrance
- Study dates
- 10 Oct 2014to 15 May 2017
- Phase
- Phase 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Man or woman
- Age ≥ 18 and ≤ 80 years
- Performance status of 0 or 1 according to the ECOG score of WHO
- Patient with Metastatic colorectal non-curative and progression on therapy in first -line therapy containing 5-fluorouracil and bevacizumab cancer.
- Patient with low or intermediate risk defined by modified Kohne's criteria
- Hepatic metastases ≥ 1 cm
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- Evaluation Review (CT chest, abdomen and pelvis ) made in the previous 4 weeks and showing the presence of a measurable lesion according to RECIST 1.1 criteria.
- Indication treatment LV5FU2 + bevacizumab validated
- Patient whose understanding of the study is good
- Biological values within the following limits :
- Bilirubin ≤ 1.5 x upper limit of normal ( N)
- AST and ALT ≤ 5 N
- Creatinin ≤ 1.5 N and creatinin clearance > 60 ml / min
- Neutrophils ≥ 1.5 . 109 / L
- Platelets ≥ 100 . 109 / L
- Hemoglobin ≥ 9 g / dL ( even if includable patients were transfused ) .
- Albumin ≥ 30 g / L
- Serological hepatitis B , C and HIV negative
- Information given and signed informed consent
- Patient affiliated to a social security system
- For women of childbearing age , the need for effective contraception.
Who cannot join
- Related to the disease:
- Other cancer within 5 years prior to entry into the trial or concomitant (except carcinoma in situ of the cervix or basal cell carcinoma of the skin ) .
- Presence of brain metastasis
- Prognosis estimated survival <3 months
- Related to treatment :
- Presence of a contraindication to bevacizumab ( major surgery in the previous 28 days , the risk of arterial thrombosis, risk of bleeding , deep vein thrombosis without effective anti- coagulant treatment or unbalanced anticoagulant treatment) Concomitant systemic
Show all 19Show fewer
- Immunotherapy , immunosuppressants, corticosteroids ≥ 1mg/kg or hormone therapy : corticosteroids administered chronically , immunosuppressive therapy, biotherapy administered under the management of inflammatory disease (anti -TNF , anti- IL6 ... )
- Hypersensitivity to one of the compounds of treatments
- Latex Hypersensitivity ( the cap of the syringe containing anakinra contains dry natural rubber, a derivative of latex), which may cause allergic reactions
- Peripheral neuropathy grade ≥ 2
- History of autoimmune disease or inflammatory
- Related to patient conditions :
- Participation during or within 30 days prior to study entry to another clinical trial with an experimental molecule.
- Serious disease unbalanced, underlying infection that may prevent the patient from receiving treatment
- Intestinal occlusion or sub- occlusion or history of inflammatory bowel disease
- Pregnancy (test mandatory inclusion pregnancy) , lactation or lack of effective contraception for men and women of childbearing age
- Psychiatric disease compromising understanding of the information or the accomplishment of the study
- Patient under guardianship, curatorship or judicial protection
- Unable to sign the informed consent or to submit to medical follow-up for geographical, social or psychological reasons.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study Evaluating the Influence of LV5FU2 Bevacizumab Plus Anakinra Association on Vascularization of Liver Metastases of Metastatic Colorectal Cancer: Proof of Concept Study
The metastatic colon cancer is a major public health problem despite advances in chemotherapy; few new drugs are in development for the treatment of this pathology.
Many studies have shown that human colon cancer is a tumor that is recognized by the immune system and the presence of lymphocytic infiltrates in the tumor bed is associated with a better prognosis. Conversely, the effect of chemotherapy on the immune response is little studied.
Read more
Recently the importance of myeloid suppressor cells (MDSC) in the development of colon cancer and the effect of 5- fluorouracil on this cell population has been highlighted. An accumulation of these cells in the blood and lymphoid organs during tumor progression is observed. Moreover, it has been established that the death of MDSC induced by 5-fluorouracil induces activation of caspase -1 and IL-1beta by these MDSC.
These events promote the polarization of CD4 T cells in intratumoral Th17 lymphocytes. The IL- 17 produced by these cells exerts a pro-angiogenic effect in inducing proliferation of endothelial cells expressing and thus limits the effect of 5- fluorouracil endoglin.
In humans, it has also been observed that chemotherapy using 5- fluorouracil and in particular LV5FU2 association +/- bevacizumab induces rapid death of blood MDSC as well as activation of caspase 1 in these cells. Thus, production of IL - 1 is detected in the serum of patients after 24 hours of the administration of 5-fluorouracil.
Chronic inflammation and the production of interleukin- 1 can alter the effectiveness of anti -tumor immune responses and facilitate angiogenesis. Many preclinical data suggest a role of anti -tumor inhibition of IL- 1beta, but the effect of a combination of chemotherapy and an inhibitor of IL - 1beta has not yet been tested in human.
Anakinra is a drug used in humans for many years to treat signs and symptoms of rheumatoid arthritis. In combination with methotrexate, in patients whose response to methotrexate alone is not satisfactory it had shown interesting results. The dose used clinically is 100 mg per day which is the dose that is proposed to be tested in this study.
In this context it should be remembered that methotrexate is a chemotherapeutic agent from the class of antimetabolites such as 5- fluorouracil.
RCP of this drug indicate that in studies originator toxicity was similar between the control arm and anakinra arm with an increase in serious infections (1.8 % vs 0.7 %) and an increased incidence of neutropenia (2.5 % neutropenia > grade = 1). The main toxicity observed is a painful inflammatory reaction at the injection site in 70 % of patients The investigators believe that this project could permit to validate in man preclinical observations showing an anti-tumor potential for combination anakinra and 5 fluorouracil.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- ANAKINRA
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANAKINRADrug
| Study group | Role | What they receive |
|---|---|---|
| ANAKINRA | Experimental | LV5FU2 + bevacizumab + anakinra Receives: Drug: ANAKINRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate after 2 months in patients with colorectal cancer with liver metastases treated with anakinra and LV5FU2/bevacizumab
Measured: after 2 months of treatment
Secondary outcomes (4)
Response rate by echography
Measured: 15 days after the beggining of treatment
Tumor control rate
Measured: At 2, 4, 6, 9 and 12 months after the beginning of treatment
Overall survival
Measured: At 2, 4, 6, 9 and 12 months after the beginning of treatment
Rate and safety profile according to NCI-CTCAE v4
Measured: Every 15 days before each cycle of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study start10 Oct 2014
- Primary completion10 Oct 2014
- Study completion15 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Georges Francois Leclerc
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02090101
- Sponsor's protocol ID
- 2013-003367-55
- Acronym
- IRAFU
- Status last verified
- Oct 2023
- First submitted
- 13 Mar 2014
- Last updated
- 17 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating the Influence of LV5FU2 Bevacizumab Plus Anakinra Association on Vascularization of Liver Metastases of Metastatic Colorectal Cancer: Proof of Concept Study
- ClinicalTrials.gov ID
- NCT02090101
- Acronym / sponsor ID
- IRAFU / 2013-003367-55
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Centre Georges Francois LeclercUniversity, hospital or other
- Study start
- 10 Oct 2014 (actual)
- Primary completion
- 10 Oct 2014 (actual)
- Study completion
- 15 May 2017 (actual)
- First posted
- 18 Mar 2014 (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 metastatic colon cancer is a major public health problem despite advances in chemotherapy; few new drugs are in development for the treatment of this pathology.
Many studies have shown that human colon cancer is a tumor that is recognized by the immune system and the presence of lymphocytic infiltrates in the tumor bed is associated with a better prognosis. Conversely, the effect of chemotherapy on the immune response is little studied.
Recently the importance of myeloid suppressor cells (MDSC) in the development of colon cancer and the effect of 5- fluorouracil on this cell population has been highlighted. An accumulation of these cells in the blood and lymphoid organs during tumor progression is observed. Moreover, it has been established that the death of MDSC induced by 5-fluorouracil induces activation of caspase -1 and IL-1beta by these MDSC.
These events promote the polarization of CD4 T cells in intratumoral Th17 lymphocytes. The IL- 17 produced by these cells exerts a pro-angiogenic effect in inducing proliferation of endothelial cells expressing and thus limits the effect of 5- fluorouracil endoglin.
In humans, it has also been observed that chemotherapy using 5- fluorouracil and in particular LV5FU2 association +/- bevacizumab induces rapid death of blood MDSC as well as activation of caspase 1 in these cells. Thus, production of IL - 1 is detected in the serum of patients after 24 hours of the administration of 5-fluorouracil.
Chronic inflammation and the production of interleukin- 1 can alter the effectiveness of anti -tumor immune responses and facilitate angiogenesis. Many preclinical data suggest a role of anti -tumor inhibition of IL- 1beta, but the effect of a combination of chemotherapy and an inhibitor of IL - 1beta has not yet been tested in human.
Anakinra is a drug used in humans for many years to treat signs and symptoms of rheumatoid arthritis. In combination with methotrexate, in patients whose response to methotrexate alone is not satisfactory it had shown interesting results. The dose used clinically is 100 mg per day which is the dose that is proposed to be tested in this study.
In this context it should be remembered that methotrexate is a chemotherapeutic agent from the class of antimetabolites such as 5- fluorouracil.
RCP of this drug indicate that in studies originator toxicity was similar between the control arm and anakinra arm with an increase in serious infections (1.8 % vs 0.7 %) and an increased incidence of neutropenia (2.5 % neutropenia > grade = 1). The main toxicity observed is a painful inflammatory reaction at the injection site in 70 % of patients The investigators believe that this project could permit to validate in man preclinical observations showing an anti-tumor potential for combination anakinra and 5 fluorouracil.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ANAKINRA | Experimental | Drug: ANAKINRALV5FU2 + bevacizumab + anakinra |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Man or woman
- Age ≥ 18 and ≤ 80 years
- Performance status of 0 or 1 according to the ECOG score of WHO
- Patient with Metastatic colorectal non-curative and progression on therapy in first -line therapy containing 5-fluorouracil and bevacizumab cancer.
- Patient with low or intermediate risk defined by modified Kohne's criteria
Key exclusion criteria (19 listed)
- Other cancer within 5 years prior to entry into the trial or concomitant (except carcinoma in situ of the cervix or basal cell carcinoma of the skin ) .
- Presence of brain metastasis
- Prognosis estimated survival <3 months
- Presence of a contraindication to bevacizumab ( major surgery in the previous 28 days , the risk of arterial thrombosis, risk of bleeding , deep vein thrombosis without effective anti- coagulant treatment or unbalanced anticoagulant treatment) Concomitant systemic
- Immunotherapy , immunosuppressants, corticosteroids ≥ 1mg/kg or hormone therapy : corticosteroids administered chronically , immunosuppressive therapy, biotherapy administered under the management of inflammatory disease (anti -TNF , anti- IL6 ... )
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 |
|---|---|---|
| ANAKINRA | Drug | ANAKINRA |
Primary outcome
Response rate after 2 months in patients with colorectal cancer with liver metastases treated with anakinra and LV5FU2/bevacizumab
Time frame: after 2 months of treatment
4 secondary outcomes
Response rate by echography
Time frame: 15 days after the beggining of treatment
Tumor control rate
Time frame: At 2, 4, 6, 9 and 12 months after the beginning of treatment
Overall survival
Time frame: At 2, 4, 6, 9 and 12 months after the beginning of treatment
Rate and safety profile according to NCI-CTCAE v4
Time frame: Every 15 days before each cycle of treatment
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 17 Oct 2023.
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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 2 study testing ANAKINRA in people with Metastatic Colorectal Cancer, run by Centre Georges Francois Leclerc 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 21 inclusion and 19 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 17 Oct 2023. 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 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?
Response rate after 2 months in patients with colorectal cancer with liver metastases treated with anakinra and LV5FU2/bevacizumab (time frame: after 2 months of treatment). 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 17 Oct 2023.