NCT05375708

Systemic Therapy in Combination with Stereotactic Radiotherapy in Patients with Metastatic Colorectal Cancer Up to 10 Metastatic Sites

A Multicenter Phase II Randomized Trial to Evaluate Systemic Therapy Versus Systemic Therapy in Combination with Stereotactic Radiotherapy in Patients with Metastatic Colorectal Cancer

• Status: Suspended
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 93 (estimated)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A small number of colorectal cancer patients with limited oligometastases may be candidates for local treatment of metastases (e.g., resection, ablation). However, it is unclear if patients with more extensive metastatic disease benefit from local therapies to control visible metastasis. The purpose of this study is to assess the impact of stereotactic body radiation therapy (SBRT) in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with metastatic colorectal cancer (mCRC) and ≤10 metastases.

Detailed description

The addition of stereotactic body radiation therapy (SBRT) to metastases in a limited unresectable metastatic setting might improve progression-free survival (PFS). The success of the addition of local treatments in mCRC patients depends largely on: control of microscopic disease, diagnostic accuracy of macroscopic disease and effective treatment of all detected metastases with limited additional toxicity to surrounding tissues. Until shortly, the use of SBRT was possible to a limited number of locations due to target movement or toxicity to surrounding radiosensitive structures. With the introduction of MRI-guided radiotherapy these limitations have been largely reduced due to the possibility to make a daily new treatment plan based on MRI-visualized anatomy. This allows the use of smaller margins for uncertainty with less healthy tissues in the radiation field. Thereby, a broader application of SBRT to add local control to metastases became possible. This study is an open-label, multicenter, randomized phase II screening trial assessing the impact of SBRT in combination with systemic therapy compared to systemic therapy alone on safety and efficacy in patients with mCRC and ≤10 metastases with no option of local treatment with curative intent and with stable disease or partial response after treatment of CAPOX-B, FOLFOX-B or FOLFOXIRI-B.

Conditions

• Metastatic Colorectal Cancer
• Oligometastatic Disease

Interventions

Type	Name	Description
RADIATION	Stereotactic body radiation therapy (SBRT)	Patients will receive a single fraction of 15 Gy to each of the macroscopic tumor sites including the primary tumor if still in situ. All lesions are treated. The treatment will be delivered in an image-guided way, either on a conventional linear accelerator (LINAC) or a MR-LINAC, whichever has the best targeting according to the treating radiation oncologist.
DRUG	Maintenance therapy (CAP-B or 5-FU/LV plus bevacizumab.)	CAP + bevacizumab (following CAPOX-B) Bevacizumab 7.5mg/kg i.v. on day 1 and 1250 mg/m2 of capecitabine, orally twice daily on days 1-14 if age is \<70 years and 1000 mg/m2 of capecitabine, orally twice daily on days 1-14 if age is higher than 70 years. CAP + bevacizumab is repeated every three weeks. 5-FU/LV + bevacizumab (following FOLFOX-B) Bevacizumab 5.0mg/kg i.v. together with leucovorin 400 mg/m2 i.v. bolus 5FU 400 mg/m2 all on day 1. Followed by continuous infusion of 5-fluorouracil 2400 mg/m2 in 46 hours. 5-FU + bevacizumab is repeated every two weeks. 5-FU/LV + bevacizumab (following FOLFOXIRI-B) Bevacizumab 5.0mg/kg i.v. together with leucovorin 400 mg/m2 i.v. all on day 1. Followed by continuous infusion of 5-fluorouracil 3200 mg/m2 in 46 hours. 5-FU + bevacizumab is repeated every two weeks. When S1 is used a replacement for fluoropyrimidine therapy it is administered in a dose of 30mg/m2 twice daily on days 1-14. S1 is repeated every three weeks.

Timeline

• Start date: 2025-12-01
• Primary completion: 2031-06-01
• Completion: 2034-06-01
• First posted: 2022-05-17
• Last updated: 2025-03-28

Locations

4 sites across 1 country: Netherlands