Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation

Sponsor
Ludwig-Maximilians - University of Munich
Study ID
NCT04034173
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

  • Treatment Related Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Panitumumab — DRUG
    Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.
  • Irinotecan — DRUG
    Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
  • Folinic acid — DRUG
    Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
  • 5-FU — DRUG
    5-FU 400 mg/m² BSA, bolus, D1 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2

Study Details

The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster development of resistance when sensitive cells are eradicated and when the RAS-mutant anti-EGFR resistant clones become predominant. The characteristics of low-level RAS mutant tumors would be: * Objective response rate (ORR) high (reflecting the sensitive clone) * Progression-free survival (PFS) short (reflecting the more rapid outgrowth of RAS mutant clones)

Key Dates

Start date
Aug 1, 2019
Status verified
Jul 2019
Primary completion
Aug 1, 2024
Completion
Aug 1, 2026

Study Design

Enrollment
120 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: RAS mutations frequency <= 7%
    Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14
  • Other: RAS mutation frequency >7% to <=14%
    Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14
  • Other: RAS mutation frequency >14% to <=20%
    Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1 \*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes. Followed by FOLFIRI regimen * Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1 * Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1 * 5-FU 400 mg/m² BSA, bolus, D1 * 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2 q day 14

Primary Outcome Measure

Overall Response Rate [ Time Frame: up to 60 months ]

Central Contacts