Radioembolization in Elderly/ Fragile Patients With mCRC (CAIRO7)

Radioembolization in Elderly/Fragile Patients With Unresectable Livermetastases of Colorectal Cancer, CAIRO7 Study of the DCCG

Radioembolization (RE) is a minimally invasive treatment with administration of radioactive microspheres into the hepatic artery via a microcatheter. Since tumors are preferentially supplied by the hepatic artery, most microspheres get trapped in the tumor. RE has been shown a feasible and safe procedure for the treatment of unresectable CRC liver metastases. These data compare favourably with the toxicity data of capecitabine plus bevacizumab, but this should be validated in a prospective study.

The proposed study investigates the efficacy of RE as an alternative, better tolerated and more cost-effective treatment option in elderly or frail patients compared to chronic systemic treatment with comparable progression-free survival.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Standard of care first-line systemic therapy; Device: radioembolization

Detailed Description

Rationale In The Netherlands, ±14.000 people/year are diagnosed with colorectal cancer (CRC), and 50% of patients already have/will develop distant metastases, most commonly to the liver. Standard treatment is palliative systemic treatment, which prolongs overall survival (OS). In only a small subset of patients with liver-only metastases, local treatment (i.e. surgery) of metastases is possible with curative intent, either initially or after downsizing by intensive systemic treatment. The average age at CRC diagnosis is 69 yrs, and 30% of CRC patients are ≥75 yrs. Thus, many patients are too old and/or fragile to allow intensive systemic regimens or major surgery. In frail/elderly patients the standard treatment is capecitabine plus an antibody against the vascular endothelial growth factor (VEGF, i.e. bevacizumab or biosimilar), given until disease progression or unacceptable toxicity, resulting in a median progression free survival (PFS) of 8.5-9.2 months. Capecitabine-induced hand-foot syndrome and diarrhoea are the most commonly occurring toxicities. Prolonged exposure to CTCAE grade 2 toxicity in frail or elderly patients may already significantly impact quality of life and daily functioning. Therefore, treatments with less toxicity would be of great value for these patients.

Radioembolization (RE) is a minimally invasive treatment with administration of radioactive microspheres into the hepatic artery via a microcatheter. Since tumors are preferentially supplied by the hepatic artery, most microspheres get trapped in the tumor. RE has been shown a feasible and safe procedure for the treatment of unresectable CRC liver metastases. These data compare favourably with the toxicity data of capecitabine plus bevacizumab, but this should be validated in a prospective study.

The proposed study investigates the efficacy of RE as an alternative, better tolerated and more cost-effective treatment option in elderly or frail patients compared to chronic systemic treatment with comparable progression-free survival.

Objectives:

Primary objective:

The objective of this randomized phase 2 study is to demonstrate efficacy of a single RE in terms of PFS in CRC patients with liver-only metastases who are candidates for palliative systemic treatment with capecitabine plus anti-VEGF antibody (bevacizumab or biosimilar).

Secondary objectives:

• To evaluate safety/toxicity.
• To evaluate cost-effectiveness.
• To evaluate quality of life (QoL).
• To evaluate overall survival.

Study design:

Multi-center, interventional, treatment, randomized phase 2, open label, comparative study. The study will be conducted within the network of the Dutch Colorectal Cancer Group (DCCG). Patients will be randomized 1:1 between RE and systemic treatment with capecitabine + anti-VEGF antibody.

Study population:

220 elderly and/or fragile patients with liver-limited, unresectable metastatic colorectal cancer, previously not systemically treated, who are candidates for systemic treatment with capecitabine plus an anti-VEGF antibody, will be enrolled in this study. Given the lack of validated selection criteria for elderly and/or frail this judgement will be left to the discretion of the local investigator.

Intervention:

Individualized holmium-166 radioembolization (166Ho-RE) will be performed via a catheter during angiography. Dosimetry-based treatment planning will be individualized using Q-Suite™ software. The comparator, standard systemic treatment, will be given by the local investigator and will consist of capecitabine orally 1000 mg/m2 bid day 1-14 + anti-VEGF antibody i.v. 7.5 mg/kg day 1 at 3-weekly cycles, continued until disease progression or unacceptable toxicity.

Main study parameters/endpoints:

Primary endpoint:

Progression-free survival.

Secondary endpoints:

• Safety/toxicity.
• Cost-effectiveness.
• QoL.
• Overall survival.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht
    • Utrecht, Utrecht, Netherlands, 3584 CX
      • UMC Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must have given written informed consent.
2. Female or male patients aged ≥18 years.
3. Metastatic colorectal cancer, with metastases confined to the liver, previously not systemically treated.
4. Previous local treatment of liver metastases by resection of a maximum of two liver segments and/or local ablation is allowed.
5. Elderly/frail patients, according to the local investigator not eligible for local treatments or intensive systemic regimens with combination chemotherapy.
6. ECOG Performance status 0-2 (Table 1).
7. Eligible for systemic treatment with capecitabine + anti-VEGF antibody.
8. Adequate bone marrow (Hb ≥ 6 mmol/L, WBC ≥ 3x109/L, platelets ≥ 100x109/L), liver (serum bilirubin ≤ 1x upper limit of normal (ULN), ASAT/ALAT ≤ 5x ULN), and renal (GFR ≥ 40 ml/min) functions.

Exclusion Criteria:

1. Previous systemic treatment for metastatic disease.
2. Previous adjuvant treatment completed within 6 months prior to randomization.
3. Symptoms of primary tumour, if in situ, that require intervention; prior treatment with (chemo)radiotherapy and/or resection of primary tumor is allowed.
4. Resection of more than 2 liver segments, 2-stage procedures and/or radiotherapy of liver metastases.
5. Eligible for more intensive systemic regimens (i.e. doublet or triplet chemotherapy).
6. Eligible for local treatment of liver metastases (e.g. surgical resection, ablation).
7. Presence of extrahepatic metastases; the presence of small (≤ 1 cm) lesions outside the liver on CT scan that are not clearly suspicious for metastases and/or the presence of enlarged hilar lymph nodes in the liver up to a maximal diameter of 2 cm is allowed.
8. Non-correctable INR >2.0.
9. Any serious comorbidity preventing the safe administration of anti-VEGF antibody treatment. This includes uncontrolled hypertension or treatment with ≥3 antihypertensive drugs, arterial (cerebro)vascular event within the past 12 months, history of bleeding, history of GI perforation, or presence of fistulae.
10. Pregnancy or breastfeeding.
11. Mental disorders that may compromise patient compliance.
12. Active second malignancy within the previous 5 years, with the exception of adequately treated basal cell carcinoma of skin and in situ carcinoma of cervix.
13. Body weight over 150 kg (because of maximum table load).
14. Known severe allergy for intravenous contrast fluids.
15. Participation to another investigational study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care first-line systemic therapy; capecitabine plus anti-VEGF antibody	Drug: Standard of care first-line systemic therapy; Capecitabine plus anti-VEGF antibody
Experimental: Radioembolization; radioembolization of liver with holmium-166 microspheres	Device: radioembolization; holmium-166 microspheres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		5 years
Adverse event frequency and grade according to CTCAE version 5.0		3.5 years
Quality of life (EORTC quality of life questionnaire number C30)	For all questionnaires the official manuals will be used to calculate the subscales.	3.5 years
Quality of life (EORTC quality of life questionnaire number CR29)	For all questionnaires the official manuals will be used to calculate the subscales.	3.5 years
Quality of life (Multidimensional Fatigue Inventory: MFI-20)	For all questionnaires the official manuals will be used to calculate the subscales.	3.5 years
Cost-effectiveness: Medical Consumption Questionnaire (MCQ)	For all questionnaires the official manuals will be used to calculate the subscales.	4 years
Cost-effectiveness: Productivity Cost Questionnaire (PCQ)	For all questionnaires the official manuals will be used to calculate the subscales.	4 years

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Dutch Colorectal Cancer Group

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): September 1, 2025
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CAIRO7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No