Metastatic Colorectal CancerPhase 2IMMUNOXNCT04430985
FOLFOX + Immunotherapy With Intrahepatic Oxaliplatin for Patients With Metastatic Colorectal Cancer
A Phase 2 study testing Oxaliplatin, 5-Fluorouracil and Leucovorin in people with Metastatic Colorectal Cancer, run by Dorte Nielsen at 1 site in Denmark.
Trial summary
In this trial chemotherapy regimen FOLFOX with intrahepatic administration of oxaliplatin is combined with immunotherapy (nivolumab and ipilimumab) for the group of patients with multiple liver metastasis from colorectal cancer. Investigators hope to increase the disease-free survival after 3 years from 10 % to 30%. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Oxaliplatin, 5-Fluorouracil and Leucovorin
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteDenmark
- Study dates
- 30 Sep 2020to 6 Sep 2021
- 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 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent
- Age: 18 - 79 years
- Performance status 0-1.
- Histologically documented colorectal cancer (In case primary tumor has not yet been removed, it should be possible to be removed by surgery)
- Tumor is immunohistochemically microsatellite stable (MSS)
- More than 5 liver metastasis, not eligible for liver resection or radiofrequency ablation (RFA)
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- Presence of liver metastasis documented on CT-scan with no documented extrahepatic disease except from primary tumor in situ.
- Measurable disease according to RECIST 1.1
- Involved liver tissue under 70 %
- Perfusion of liver metastasis possible via a. hepatica
- ANC >= 1,5 x 10¨9/ml og Platelets >= 100 x 10¨9/ml ,
- Estimated creatinine clearance >= 60 ml/min
- INR < 1,4 and bilirubin <= 1,5 x ULN
Who cannot join
- Current or prior second malignancy within 5 years, except from basal cell carcinoma or carcinoma in situ cervix uteri.
- Severe medical condition, such as severe cardiac disease or AMI within 1 year
- Uncontrolled infection.
- Patients positive for HIV, HBV-sAG or HCV antibody
- Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of ipilimumab, nivolumab. The following are exceptions to this criterion:
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- Intranasal, inhaled, or topical steroids; or local steroid injections (e.g. intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
- Patients requiring treatment with oral prednisolon of dose > 10 mg daily
- Previous severe, unexpected reaction related to treatment with fluoropyrimidine.
- Previous treatment with oxaliplatin or immunotherapy
- Neuropathy that is contraindicated for treatment with oxaliplatin
- Pregnant or breastfeeding women. Women with childbearing potential (WOCBP) should have a negative pregnancy test and agree to use highly effective method(s) of contraception during treatment and 6 months thereafter.
- Men who are sexually active with WOCBP who do not agree to use highly effective method(s) of contraception during treatment and 7 months after immunotherapy or 6 months after chemotherapy (which period is the longest)
- Patients who, for linguistic, intellectual or cultural reasons, will not be able to fully understand the concept of treatment and respond to any. complications.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: FOLFOX + Immunotherapy With Intrahepatic Administration of Oxaliplatin for Patients With Multiple Non-resectable Liver Metastasis From Colorectal Cancer
In this trial chemotherapy regimen FOLFOX with intrahepatic administration of oxaliplatin is combined with immunotherapy (nivolumab and ipilimumab) for the group of patients with multiple liver metastasis from colorectal cancer. Investigators hope to increase the disease-free survival after 3 years from 10 % to 30%.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Oxaliplatin, 5-Fluorouracil, Leucovorin, Nivolumab, Ipilimumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Day 1 in cycle 1-4: 100 mg/m2 intrahepatic administration Day 1 in cycle 5-8: oxaliplatin 85 mg/m2 i.v.
5-FluorouracilDrug
Day 1 each cycle: 400 mg/m2 i.v. bolus, 2400 mg/m2 i.v.over 46 hrs
LeucovorinDrug
Day 1 each cycle: 400 mg/m2 i.v.
NivolumabDrug
Day 3 in cycle 3 to 8: 3 mg/kg i.v.
IpilimumabDevice
Day 3 in cycle 3 and 6: 1 mg/kg i.v.
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX + Immunotherapy | Experimental | 8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6)
Immunotherapy:
Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations) Receives: Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Nivolumab; Device: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free Survival at 3 years
Proportion of patients without signs of disease 3 years after treatment start
Measured: 3 years from start of treatment within the trial
Secondary outcomes (5)
Patients becoming eligible for resection of liver metastasis
Number of patients with reduction of tumor burden to an extent that they become eligible for resection/radio frequency ablation of liver metastasis
Measured: Evaluation of resectability after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Objective response rate
Proportion of patients with complete or partial response according to RECIST v1.1
Measured: Evaluation by CT-scan after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Progression free survival
Time from start of treatment to progression of disease or death
Measured: Evaluation by CT-scan after 8 cycles of treatment each cycle is 14 days) and every 3 months thereafter until progression (max 3 years)
Overall survival
Time from start of treatment to death
Measured: Survival follow-up is planned for at least 3 years from treatment start
Safety and tolerability of the treatment
Incidence of treatment related Adverse Events
Measured: During the 16 weeks of treatment and 100 days thereafter (up to 31 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start30 Sep 2020
- Primary completion6 Sep 2021
- Study completion6 Sep 2021
Why it stopped: Problems identifying eligble patients
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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dorte Nielsen
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Cancer Society
- Responsible party
- Sponsor-investigator, Dorte Nielsen, Herlev Hospital
- Investigators
- Ole Larsen, MD, PhD, Principal investigator, Herlev Hospital, Department of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04430985
- Sponsor's protocol ID
- GI 1949
- Other IDs
- 2019-004397-26, 2019
- Acronym
- IMMUNOX
- Status last verified
- Oct 2021
- First submitted
- 8 Jun 2020
- Last updated
- 27 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FOLFOX + Immunotherapy With Intrahepatic Administration of Oxaliplatin for Patients With Multiple Non-resectable Liver Metastasis From Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04430985
- Acronym / sponsor ID
- IMMUNOX / GI 1949
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Problems identifying eligble patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dorte NielsenUniversity, hospital or other
- Collaborators
- Danish Cancer Society
- Study start
- 30 Sep 2020 (actual)
- Primary completion
- 6 Sep 2021 (actual)
- Study completion
- 6 Sep 2021 (actual)
- First posted
- 16 Jun 2020 (actual)
- 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.
In this trial chemotherapy regimen FOLFOX with intrahepatic administration of oxaliplatin is combined with immunotherapy (nivolumab and ipilimumab) for the group of patients with multiple liver metastasis from colorectal cancer. Investigators hope to increase the disease-free survival after 3 years from 10 % to 30%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FOLFOX + Immunotherapy | Experimental | Drug: Oxaliplatin, Drug: 5-Fluorouracil, Drug: Leucovorin, Drug: Nivolumab, Device: Ipilimumab8 cycles of FOLFOX every 2 weeks with intrahepatic administration of oxaliplatin in cycles 1-4, thereafter (cycles 5-8) oxaliplatin i given i.v.; starting from cycle 3 this is combined with i.v. administration of nivolumab (cycle 3-8) and ipilimumab (cycle 3 + 6) Immunotherapy: Starting from cycle 3: Nivolumab 3 mg/kg i.v. on day 3 (every 2nd week, total of 6 administrations), Ipilimumab 1 mg/kg i.v. on day 3 (every 6th week, total of 2 administrations) |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Informed consent
- Age: 18 - 79 years
- Performance status 0-1.
- Histologically documented colorectal cancer (In case primary tumor has not yet been removed, it should be possible to be removed by surgery)
- Tumor is immunohistochemically microsatellite stable (MSS)
Key exclusion criteria (16 listed)
- Current or prior second malignancy within 5 years, except from basal cell carcinoma or carcinoma in situ cervix uteri.
- Severe medical condition, such as severe cardiac disease or AMI within 1 year
- Uncontrolled infection.
- Patients positive for HIV, HBV-sAG or HCV antibody
- Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
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 |
|---|---|---|
| OxaliplatinDay 1 in cycle 1-4: 100 mg/m2 intrahepatic administration Day 1 in cycle 5-8: oxaliplatin 85 mg/m2 i.v. | Drug | FOLFOX + Immunotherapy |
| 5-FluorouracilDay 1 each cycle: 400 mg/m2 i.v. bolus, 2400 mg/m2 i.v.over 46 hrs | Drug | FOLFOX + Immunotherapy |
| LeucovorinDay 1 each cycle: 400 mg/m2 i.v. | Drug | FOLFOX + Immunotherapy |
| NivolumabDay 3 in cycle 3 to 8: 3 mg/kg i.v. | Drug | FOLFOX + Immunotherapy |
| IpilimumabDay 3 in cycle 3 and 6: 1 mg/kg i.v. | Device | FOLFOX + Immunotherapy |
Primary outcome
Disease-free Survival at 3 years
Time frame: 3 years from start of treatment within the trial
Proportion of patients without signs of disease 3 years after treatment start
5 secondary outcomes
Patients becoming eligible for resection of liver metastasis
Time frame: Evaluation of resectability after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Objective response rate
Time frame: Evaluation by CT-scan after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Progression free survival
Time frame: Evaluation by CT-scan after 8 cycles of treatment each cycle is 14 days) and every 3 months thereafter until progression (max 3 years)
Overall survival
Time frame: Survival follow-up is planned for at least 3 years from treatment start
Safety and tolerability of the treatment
Time frame: During the 16 weeks of treatment and 100 days thereafter (up to 31 weeks)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2021.
- Individual participant dataSharing planned: No
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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.
Ole Larsen, MD, PhD principal investigator
Herlev Hospital, Department of Oncology
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 Oxaliplatin, 5-Fluorouracil and Leucovorin in people with Metastatic Colorectal Cancer, run by Dorte Nielsen at 1 site in Denmark.
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 13 inclusion and 16 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: withdrawn, as of the sponsor's last update on 27 Oct 2021. 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 Denmark. 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 was withdrawn before enrolling participants, so there are no results.
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?
Disease-free Survival at 3 years (time frame: 3 years from start of treatment within the trial). 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 Oct 2021.