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Evaluating a combination treatment for liver-dominant metastatic colorectal cancer

A Prospective, Multicenter, Open-label, Phase II Study to Evaluate Efficacy and Safety of Selective Internal Radiation Therapy Plus Xelox, Bevacizumab and Atezolizumab (Immune Chekpoint Inhibitor) in Patients With Liver-dominant Metastatic Colorectal Cancer

Phase 2 Interventional Federation Francophone de Cancerologie Digestive · NCT04659382

This study is testing a new combination of treatments for people with liver-dominant metastatic colorectal cancer to see if it can help control their disease better.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment52 (estimated)
Ages18 Years and up
SexAll
SponsorFederation Francophone de Cancerologie Digestive Academic / other
Drugs / interventionsbevacizumab, chemotherapy, radiation, prednisone, Atezolizumab
Locations19 sites (Amiens and 18 other locations)
Trial IDNCT04659382 on ClinicalTrials.gov

What this trial studies

This study aims to assess the safety and efficacy of a combination treatment involving selective internal radiation therapy (SIRT), chemotherapy (XELOX), anti-angiogenic therapy (Bevacizumab), and an immune checkpoint inhibitor (Atezolizumab) in patients with liver-dominant metastatic colorectal cancer. It is a single-arm, prospective, multi-center phase II study focusing on patients with mismatch repair proficient metastatic colorectal cancer who have unresectable liver metastases. The study seeks to induce both local and systemic immune responses to improve disease control in the liver and potentially in extra-hepatic sites as well.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed mismatch repair proficient metastatic colorectal cancer and predominantly liver-dominant disease.

Not a fit: Patients with primarily extra-hepatic metastatic disease or those who have received prior oncologic treatment for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with liver-dominant metastatic colorectal cancer, potentially improving survival and quality of life.

How similar studies have performed: While the combination of SIRT and immune checkpoint inhibitors is a novel approach, previous studies have shown promise in using radiation to enhance the efficacy of immunotherapy in various cancers.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age ≥18 years
* Histologically proven mismatch repair proficient metastatic colorectal cancer (pMMR and/or MSS)
* Liver-dominant disease with up to 6 extrahepatic lesions (only peritoneal lesions are not allowed) if asymptomatic and without organ dysfunction.
* Measurable disease according to RECIST 1.1
* Patient with initially unresectable disease according to the local multidisciplinary team and eligible for radioembolization according to the radiologist's opinion
* Tumor volume \< 50 % of total liver volume
* No prior oncologic treatment for metastatic disease (i.e. chemotherapy, radiotherapy or investigational drug). Patients may have received adjuvant chemotherapy or (neo) adjuvant radiochemotherapy to the pelvis (tumor of the rectum), but the last dose of chemotherapy/radiotherapy must be administered at least 6 months prior to entry into this study. Analgesic radiotherapy of metastasis is permitted except on hepatic lesions and must be completed at least 14 days before inclusion.
* WHO performance status ≤ 1
* Estimated life expectancy ≥ 3 months
* Adequate hematological function: with neutrophils ≥ 1,500 /mm3, platelet count ≥ 100,000/mm3, hemoglobin \> 9 g/dL (5,6 mmol/l)
* Adequate hepatic function: hepatic transaminases (ASAT and ALAT) ≤ 5 x UNL, total bilirubin ≤ 2 x UNL, alkaline phosphatase ≤ 5 x UNL
* Adequate renal function: creatinine clearance ≥ 50 ml/min according MDRD (Modification of Diet in Renal Disease)
* Patient affiliated to a social security system Information provided to patient and signature of the informed consent form by patient and the investigator

Exclusion Criteria:

* Active infection still requiring intravenous antibiotics on the first scheduled day of protocol treatment
* Symptomatic or untreated central nervous system metastasis
* Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years,
* Other malignancy in the 5 years prior to inclusion in the study, except for localized cancer in situ, basal or squamous cell skin cancer
* Confirmed peritoneal carcinomatosis (lesions detectable on CT-scan and/or MRI)
* Active autoimmune disease or inflammatory bowel disease
* Bone marrow allograft or solid organ transplant history
* History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT-scan and any severe chronic respiratory insufficiency that the investigator believes would not allow the SIRT to be received safely
* Positive tests for HIV or other immunodeficiency syndromes
* Severe chronic liver failure, which in the investigator's opinion would not allow SIRT to be received safely
* Active hepatitis B or hepatitis C.
* Active tuberculosis
* Patient with contraindication to angiography and selective hepatic catheterization such as bleeding diathesis or coagulopathy with serious bleeding risk that is not correctable by usual therapy of hemostatic agents.
* Patients on anticoagulant therapy different from low-molecular-weight heparin (LMWH) cannot be included (i.e. VKA and NOACs). Relaying these anticoagulants to a LMWH before inclusion is allowed. In addition, it must be possible to stop the LMWH 24 hours before invasive procedures according to the usual recommendations (before the work-up and before the SIRT).
* Significant presence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis on clinical or radiological evaluation Previous radiotherapy in the upper abdominal region (liver or liver vessels in the radiation field)
* If primary tumor is non-resected, it must be asymptomatic
* Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if they receive a dose equivalent to no more than 10 mg of prednisone equivalent dose per day, and corticosteroid administration is permitted by a route resulting in minimal systemic exposure (cutaneous, rectal, articular, ocular or inhalation) is authorized)
* Partial or complete DPD deficiency
* Known hypersensitivity to any components of bevacizumab, Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies and any other contraindications to the use of investigational medicinal products, in particular patients with peripheral sensory neuropathy with functional impairment (see SmPC of oxaliplatin) or in the case of recent or concomitant treatment with brivudine (see SmPC of capecitabine)
* QT/QTc interval \> 450 msec for male and \> 470 msec for female at EKC.
* K+ \< LLN, Mg²+ \< LLN, Ca²+ \< LLN
* Allergy to contrast agents that do not allow radioembolization to be performed
* Uncontrolled hypertension (blood pressure \> 140 mm Hg and/or diastolic blood pressure \> 90 mm Hg)
* Clinically significant cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to the start of study treatment, myocardial infarction ≤ 6 months prior to the start of study treatment, unstable angina, congestive heart failure of NYHA (New York Heart Association Functional Classification) grade 2 or higher, or severe cardiac arrhythmia not controlled by drug therapy or which may interfere with study treatment
* Significant vascular disease (e.g. aortic aneurysm requiring surgery or arterial thrombosis) within 6 months prior to initiation of study treatment
* Venous thromboembolic disease within 3 months prior to initiation of study treatment
* Surgical procedure (including surgical biopsy, any surgical resection, or other major surgery) or significant traumatic injury within 28 days prior to start of study treatment, or planning major surgery during the study.
* History of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to start of study treatment
* Unhealing decaying wound, active ulcer, or untreated bone fracture
* Proteinuria ≥ 2+ by urine dipstick unless a 24-hour urine protein \< 1 g of protein is demonstrated
* Lack of effective contraception in patients (male and/or female) at risk of reproduction, pregnant or breastfeeding women and women at risk of reproduction who have not had a pregnancy test.
* Persons deprived of freedom or under guardianship
* Inability to undergo medical follow-up of the study for geographical, social or psychological reasons

Where this trial is running

Amiens and 18 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Colorectal CancerpMMRMSSImmune Checkpoint InhibitorInternal Radiotherapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.