Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer Best Supportive Care Capecitabine Fluorouracil (5-FU) Sym004
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 254
Healthy volunteers: no

Brief summary:
This is a Phase 2, open-label, randomized, 3-arm trial investigating the efficacy of two Sym004 doses (Arm A and Arm B) compared with a control group (Arm C) in subjects with metastatic colorectal cancer (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs).

Detailed description:
This trial assesses the efficacy of two different weekly dosing regimens of Sym004 (Arm A: 12 mg/kg/week versus Arm B: 9 mg/kg loading dose followed by 6 mg/kg/week) compared with investigator's choice in terms of overall survival time in subjects with mCRC. Subjects assigned to Arm C will receive best supportive care (BSC), Fluorouracil (5-FU), or Capecitabine, per local standard of care.

Subjects will receive treatment until unacceptable toxicity, disease progression, withdrawal of consent, or until the subject meets any of the criteria for treatment discontinuation or trial discontinuation. Therefore, the duration of treatment will differ among individuals and cannot be fixed in advance.

Arms:
arm 1: Sym004 will be administered as an intravenous infusion at a dose of 12 milligrams per kilogram (mg/kg) weekly until unacceptable toxicity, disease progression, or consent withdrawal. arm 2: Sym004 will be administered as an intravenous infusion at a loading dose of 9 mg/kg followed by 6 mg/kg weekly until unacceptable toxicity, disease progression, or consent withdrawal. arm 3: Best supportive care (BSC) or Fluorouracil (5-FU) or Capecitabine will be given as per Investigator's discretion.

Interventions: intervention 1: Sym004 (12 mg/kg) intervention 2: Sym004 (9/6 mg/kg) intervention 3: Best Supportive Care (BSC) intervention 4: Fluorouracil (5-FU) intervention 5: Capecitabine
Intervention descriptions: intervention 1: Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR. intervention 2: Sym004 is a 1:1 mixture of two mAbs (futuximab and modotuximab) which bind to two non-overlapping epitopes of the EGFR. intervention 3: BSC is the best palliative care as per Investigator's discretion, excluding antineoplastic agents. BSC may include, but is not limited to, antibiotics, analgesics, antiemetics, blood transfusions, and nutritional support. intervention 4: 5-FU will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert. intervention 5: Capecitabine will be administered at doses and schedules as per Investigator's discretion and in line with the local package insert.

Protocol document: