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

Sponsor
Gruppo Oncologico del Nord-Ovest
Study ID
NCT05062889
Phase
PHASE2
Status
Suspended

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • 5-Fluorouracil continuous infusion FOLFOXIRI schedule — DRUG
    3200 mg/sqm 48 h-continuous infusion, starting on day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • 5-Fluorouracil bolus FOLFOX schedule — DRUG
    400 mg/sqm iv bolus, day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • 5-Fluorouracil continuous infusion FOLFOX schedule — DRUG
    2400 mg/sqm 48 h-continuous infusion, starting on day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • Oxaliplatin FOLFOX and FOLFOXIRI schedule — DRUG
    85 mg/sqm iv over 2 hours, day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • Oxaliplatin CAPOX schedule — DRUG
    130 mg/sqm iv over 2 hours, day 1. To be repeated every three weeks for a maximum of 8 cycles.
  • L-Leucovorin — DRUG
    200 mg/sqm iv over 2 hours, day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • Capecitabine — DRUG
    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.
  • Irinotecan — DRUG
    165 mg/sqm iv over 60 minutes, day 1. To be repeated every two weeks for a maximum of 12 cycles.
  • Trifluridine/Tipiracil — DRUG
    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.
  • Trastuzumab — DRUG
    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.
  • Tucatinib — DRUG
    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.

Study Details

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

Key Dates

Start date
May 17, 2023
Status verified
Jan 2026
Primary completion
Oct 31, 2027
Completion
Dec 31, 2029

Study Design

Enrollment
477 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm B FOLFOXIRI, part 1 (adjuvant)
    FOLFOXIRI Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluoruracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or irinotecan interruption because of adverse events, patient's refusal or investigator's choice, the continuation of the other drugs until 12 cycles is recommended.
  • Active Comparator: Arm A mFOLFOX6 or CAPOX (at investigator's choice), part 1 (adjuvant)
    mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. The continuation of 5FU/leucovorin until 12 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. CAPOX Oxaliplatin 130 mg/sqm iv over 2 hours, day 1; Capecitabine 1000 mg/sqm/bid per os from day 1 to day 14; to be repeated every 3 weeks until 8 cycles. The continuation of Capecitabine until 8 cycles is recommended also if oxaliplatin is interrupted because of adverse events, patient's refusal or investigator's choice. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery
  • Experimental: Trastuzumab and Tucatinib plus mFOLFOX6, part 1 target-driven (adjuvant)
    Tucatinib 300 mg (two 150 mg tablets)/bid orally twice daily (approximately 8 to 12 hours between doses with or without a meal); Trastuzumab 4 mg/kg iv over 30 minutes, day 1 (loading dose: 6 mg/kg iv over 90 minutes), followed by mFOLFOX6 Oxaliplatin 85 mg/sqm iv over 2 hours, day 1 in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours, day 1 followed by 5-fluorouracil 400 mg/sqm iv bolus, day 1 followed by 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. In the case of oxaliplatin and/or trastuzumab and/or tucatinib interruption because of adverse events, patient's refusal or investigator's choice, the prosecution of the other drugs until 12 cycles is recommended. Pending the results of ct-DNA analysis, up to 2 cycles of FOLFOX/CAPOX before randomization are allowed to start the adjuvant treatment within 8-10 weeks after surgery
  • Experimental: Arm B Trifluridine/Tipiracil, part 2 (post-adjuvant)
    Trifluridine/Tipiracil: 35 mg/ m2/bid per os days 1-5 and 8-12 to be repeated every 4 weeks until 6 cycles.
  • No Intervention: Arm A Observation, part 2 (post-adjuvant)
    Follow-up

Primary Outcome Measure

ct-DNA clearance rate after the end of the adjuvant treatment (ERASE-CRC part 1) [ Time Frame: 6 months from the enrollment of the last patient in the adjuvant treatment ]

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