FOLFOX + Immunotherapy With Intrahepatic Oxaliplatin for Patients With Metastatic Colorectal Cancer (IMMUNOX)

Dorte Nielsen

Status and phase: Withdrawn; Phase 2

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Oxaliplatin; Drug: Nivolumab; Device: Ipilimumab; Drug: Leucovorin; Drug: 5-Fluorouracil

Study type: Interventional

Funder types: Other

Identifiers

NCT04430985

2019-004397-26 (EudraCT Number)

GI 1949

Details and patient eligibility

About

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%.

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

FOLFOX + Immunotherapy

Experimental group

Description:

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)

Treatment:

Drug: Oxaliplatin

Drug: 5-Fluorouracil

Drug: Nivolumab

Device: Ipilimumab

Drug: Leucovorin