Immunotherapy in combination with chemotherapy with intrahepatic administration of oxaliplatin for patients with multiple liver metastasis from colorectal cancer.

Phase 1

• Conditions: iver metastasis from colorectal cancer; MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004397-26-DK
• Lead Sponsor: Department of Oncology, Herlev & Gentofte Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-19
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

- Informed cinsent
- Age: 18 – 79 years
- Performance status 0-1.
- Histologically dokumentet colorectal cancer (In case primary tumor has not yet been removed, it should be possible to be removed by surgery)
- Tumor is imminhistochemically MSS
- More than 5 liver metastaser, not eligible for liver resection or RFA
- Presence of liver metatastasis 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 clearence >= 60 ml/min
- INR < 1,4 and bilirubin <= 1,5 x ULN
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

- Current or prior second malignancy within 5 years, except from basal cell carcinoma or carcinoma in situ cervicis uteri.
- Severe medical condition, such as servere cardiac disease or AMI within 1 år
- 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 and tocilizumab. The following are exceptions to this criterion:
oIntranasal, inhaled, or topical steroids; or local steroid injections (e.g. intra-articular injection)
oSystemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
oSteroids 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 treamtment with oxaliplatin
- Pregnant or breastfeeding women. Women with childbearing potential (WOBCP) 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Disease free survival at 3 years;Secondary Objective: a) Number of patients that become eligible for liver resection/RFA during treatment due to reduced tumorburden<br>b) Progression free survival<br>c) Overall survival<br>d) Objective response rate <br>e) Safety <br><br>Exploratory translational research<br>f) immunological response in liver metastasis<br>g) Biomarker analysis ;Primary end point(s): Fraction of patients that are disease-free (without surgery/RFA of liver metastasis) at 3 years;Timepoint(s) of evaluation of this end point: 3 years after treatment start for last patient

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): a) Number of patients with tumorburden getting reduced, so patient become eligible for liver resection/RFA <br>b) Time from treatment start to PD or Death, median PFS determined using Kaplan-Meier analyses<br>c) Time from treatment start Death, median OS determined using Kaplan-Meier analyses<br>d) Objective Response (CR, PR) rate at 16 weeks<br>e) Incidence of treatment related AE ;Timepoint(s) of evaluation of this end point: At the end FU (3 years after treatment start for last patient )