NCT05062889

Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment Resected Colon Cancer Patients

Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment of Stage III and High-risk Stage II Resected Colon Cancer Patients With Adjuvant FOLFOXIRI and/or Post-adjuvant Trifluridine/Tipiracil

• Status: Suspended
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 477 (estimated)
• Sponsor: Gruppo Oncologico del Nord-Ovest · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The aims of this study are to evaluate if an intensified adjuvant treatment with FOLFOXIRI could increase the rate of cases with undetectable ct-DNA after chemotherapy and to evaluate if a further adjuvant treatment with Trifluridine/Tipiracil could increase the rate of cases with undetectable ct-DNA and therefore improve DFS in a population at high-risk of relapse. An additional target-driven cohort of HER2+ RAS wild-type colon cancer patients will be assessed for ct-DNA clearance after a tailored treatment with Trastuzumab and Tucatinib plus FOLFOX

Detailed description

This is a prospective, open-label, multicentre study, including two phase II randomized trials. In Part 1 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after surgery will be randomized to receive FOLFOX for 12 cycles or CAPOX for 8 cycles (at investigator choice) versus FOLFOXIRI for 12 cycles. In Part 1 target-driven resected stage III and high-risk stage II HER2+ and RAS wild-type colon cancer patients with positive ct-DNA after surgery will receive Trastuzumab and Tucatinib plus FOLFOX for 12 cycles. In Part 2 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after the end of a fluoropyrimidine and oxaliplatin-based adjuvant therapy - either in the frame or outside of Part 1 - will be randomized to receive observation or Trifluridine/Tipiracil for 6 cycles.

Conditions

• Stage II Colon Cancer
• Stage III Colon Cancer
• HER2-positive Colon Cancer
• RAS Wild-type Colon Cancer

Interventions

Type	Name	Description
DRUG	5-Fluorouracil continuous infusion FOLFOXIRI schedule	3200 mg/sqm 48 h-continuous infusion, starting on day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	5-Fluorouracil bolus FOLFOX schedule	400 mg/sqm iv bolus, day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	5-Fluorouracil continuous infusion FOLFOX schedule	2400 mg/sqm 48 h-continuous infusion, starting on day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	Oxaliplatin FOLFOX and FOLFOXIRI schedule	85 mg/sqm iv over 2 hours, day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	Oxaliplatin CAPOX schedule	130 mg/sqm iv over 2 hours, day 1. To be repeated every three weeks for a maximum of 8 cycles.
DRUG	L-Leucovorin	200 mg/sqm iv over 2 hours, day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	Capecitabine	Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14. To be repeated every 3 weeks until 8 cycles. Available as 500 and 150 mg tablets.
DRUG	Irinotecan	165 mg/sqm iv over 60 minutes, day 1. To be repeated every two weeks for a maximum of 12 cycles.
DRUG	Trifluridine/Tipiracil	35 mg/m2/bid per os days 1-5 and 8-12. To be repeated every 4 weeks until 6 cycles. Available as 20 and 15 mg tablets.
DRUG	Trastuzumab	4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes). To be repeated every two weeks for a maximum of 12 cycles.
DRUG	Tucatinib	300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal) for a maximum of 12 biweekly cycles.

Timeline

• Start date: 2023-05-17
• Primary completion: 2027-10-01
• Completion: 2029-12-01
• First posted: 2021-09-30
• Last updated: 2026-02-03

Locations

28 sites across 1 country: Italy