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

NCT ID: NCT04430985

Last Updated: 2021-10-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2021-09-06

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%.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOX + Immunotherapy

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)

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: DRUG

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

Intervention Type: DRUG

Day 1 each cycle: 400 mg/m2 i.v. bolus, 2400 mg/m2 i.v.over 46 hrs

Leucovorin

Intervention Type: DRUG

Day 1 each cycle: 400 mg/m2 i.v.

Nivolumab

Intervention Type: DRUG

Day 3 in cycle 3 to 8: 3 mg/kg i.v.

Ipilimumab

Intervention Type: DEVICE

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

Interventions

Oxaliplatin

Day 1 in cycle 1-4: 100 mg/m2 intrahepatic administration Day 1 in cycle 5-8: oxaliplatin 85 mg/m2 i.v.

Intervention Type: DRUG

5-Fluorouracil

Day 1 each cycle: 400 mg/m2 i.v. bolus, 2400 mg/m2 i.v.over 46 hrs

Intervention Type: DRUG

Leucovorin

Day 1 each cycle: 400 mg/m2 i.v.

Intervention Type: DRUG

Nivolumab

Day 3 in cycle 3 to 8: 3 mg/kg i.v.

Intervention Type: DRUG

Ipilimumab

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

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Cancer Society

OTHER

Sponsor Role: collaborator

Dorte Nielsen

OTHER

Sponsor Role: lead

Responsible Party

Dorte Nielsen

Professor Dorte Nielsen, MD, PhD, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ole Larsen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Herlev Hospital, Department of Oncology

Locations

Herlev University Hospital, Department of Oncology

Herlev, , Denmark

Countries

Denmark

Other Identifiers

2019-004397-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GI 1949

Identifier Type: -

Identifier Source: org_study_id