Trial Protocol of a Phase II Study of mFOLFOXIRI after Metastasectomy in Patients with Oligometastatic Colorectal...

The survival benefit of adjuvant chemotherapy after surgical resection of oligometastases from colorectal cancer (CRC) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA) was reported recently and a risk stratification strategy based on monitoring minimal/molecular residual disease (MRD) has been proposed, however, which drug regimen is most effective for ctDNA-positive patients is unknown.

Oligometastatic CRC patients planning to undergo surgery were registered in this study. After metastasectomy, the registered patients were enrolled in the treatment arm, in which 8 courses of modified-FOLFOXIRI (mFOLFOXIRI; irinotecan 150 mg/m², oxaliplatin 85 mg/m², l-leucovorin (l-LV) 200 mg/m², and 46-h continuous infusion of 5-fluorouracil (5-FU) 2400 mg/m² every 2 weeks) followed by 4 courses of 5-FU/l-LV are administered. The patients who did not meet the eligibility criteria for the treatment arm or did not consent to mFOLFOXIRI enrolled in the observation arm in which standard of care treatment is provided. Prospective blood collections for retrospective ctDNA analysis are scheduled pre-surgery, and at 28 days, 4 and 7 months after surgery. The primary endpoint is treatment compliance at 8 courses of mFOLFOXIRI and the key secondary endpoints are the ctDNA-positivity rate and survival outcomes in ctDNA-positive and -negative groups. A total of 85 patients will be enrolled from 11 institutions. First patient-in was on July 2020. Accrual completed in February 2024.

This study will potentially identify a better treatment strategy for patients with resectable oligometastatic CRC having postsurgical ctDNA positivity, compared to the current standard of care approaches.