FOLFOX + Immunotherapy With Intrahepatic Oxaliplatin for Patients With Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

— IMMUNOX  

Official title:

FOLFOX + Immunotherapy With Intrahepatic Administration of Oxaliplatin for Patients With Multiple Non-resectable Liver Metastasis From Colorectal Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04430985
• Other study ID #: GI 1949
• Secondary ID: 2019-004397-26
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 30, 2020
• Est. completion date: September 6, 2021

Study information

• Verified date: October 2021
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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%.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 6, 2021
• Est. primary completion date: September 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• 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)
• 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

Exclusion Criteria:

• 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:

• 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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Oxaliplatin
Day 1 in cycle 1-4: 100 mg/m2 intrahepatic administration Day 1 in cycle 5-8: oxaliplatin 85 mg/m2 i.v.
• 5-Fluorouracil
Day 1 each cycle: 400 mg/m2 i.v. bolus, 2400 mg/m2 i.v.over 46 hrs
• Leucovorin
Day 1 each cycle: 400 mg/m2 i.v.
• Nivolumab
Day 3 in cycle 3 to 8: 3 mg/kg i.v.

Device:
• Ipilimumab
Day 3 in cycle 3 and 6: 1 mg/kg i.v.

Locations

Country	Name	City	State
Denmark	Herlev University Hospital, Department of Oncology	Herlev

Sponsors (2)

Lead Sponsor	Collaborator
Dorte Nielsen	Danish Cancer Society

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory analysis of immunological response in tumor tissue	Composition of immune infiltrates in order to define the immune cell subsets present within FFPE tumor tissue before and after exposure to therapy.	Tumor tissue samples taken at baseline and week 16
Other	Explorative analysis of biomarkers predictive of response to the combination of nivolumab, ipilimumab in combination with FOLFOX	Biomarker analyses include, but are not limited to a range of molecules with different characteristics such as DNA, Single Nucleotide Polymorphism (SNPs), RNA, microRNA, proteins and metabolites	Blood samples are drawn at baseline through study completion (up to 3 years)
Primary	Disease-free Survival at 3 years	Proportion of patients without signs of disease 3 years after treatment start	3 years from start of treatment within the trial
Secondary	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	Evaluation of resectability after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Secondary	Objective response rate	Proportion of patients with complete or partial response according to RECIST v1.1	Evaluation by CT-scan after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
Secondary	Progression free survival	Time from start of treatment to progression of disease or death	Evaluation by CT-scan after 8 cycles of treatment each cycle is 14 days) and every 3 months thereafter until progression (max 3 years)
Secondary	Overall survival	Time from start of treatment to death	Survival follow-up is planned for at least 3 years from treatment start
Secondary	Safety and tolerability of the treatment	Incidence of treatment related Adverse Events	During the 16 weeks of treatment and 100 days thereafter (up to 31 weeks)