Clinical trial NCT04430985: FOLFOX + Immunotherapy With Intrahepatic Oxaliplatin for Patients With Metastatic Colorectal Cancer
Official title: FOLFOX + Immunotherapy With Intrahepatic Administration of Oxaliplatin for Patients With Multiple Non-resectable Liver Metastasis From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Danish Cancer Society
First posted: 2020-06-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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%.


Eligibility criteria: 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.

Primary outcomes:
measure: Disease-free Survival at 3 years
timeFrame: 3 years from start of treatment within the trial
Secondary outcomes:
measure: Patients becoming eligible for resection of liver metastasis
timeFrame: Evaluation of resectability after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
measure: Objective response rate
timeFrame: Evaluation by CT-scan after 8 cycles (each cycle is 14 days) of treatment (i.e after 16 weeks)
measure: Progression free survival
timeFrame: Evaluation by CT-scan after 8 cycles of treatment each cycle is 14 days) and every 3 months thereafter until progression (max 3 years)
measure: Overall survival
timeFrame: Survival follow-up is planned for at least 3 years from treatment start
measure: Safety and tolerability of the treatment
timeFrame: During the 16 weeks of treatment and 100 days thereafter (up to 31 weeks)
Other outcomes:
measure: Exploratory analysis of immunological response in tumor tissue
timeFrame: Tumor tissue samples taken at baseline and week 16
measure: Explorative analysis of biomarkers predictive of response to the combination of nivolumab, ipilimumab in combination with FOLFOX
timeFrame: Blood samples are drawn at baseline through study completion (up to 3 years)
Locations:
city: Herlev
country: Denmark
facility: Herlev University Hospital, Department of Oncology
Study officials:
affiliation: Herlev Hospital, Department of Oncology
name: Ole Larsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: