S1613, Trastuzumab and Pertuzumab or Cetuximab and Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic HER2/Neu Amplified Colorectal Cancer That Cannot Be Removed by Surgery

Phase 2 Completed 240 enrolled SWOG Cancer Research Network National Cancer Institute (NCI) · collab

RandomizedParallel-groupOpen-labelTreatment

Summary

This randomized phase II trial studies how well trastuzumab and pertuzumab work compared to cetuximab and irinotecan hydrochloride in treating patients with HER2/neu amplified colorectal cancer that has spread from where it started to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as trastuzumab and pertuzumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cetuximab and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trastuzumab and pertuzumab may work better compared to cetuximab and irinotecan hydrochloride in treating patients with colorectal cancer.

Timeline

Start: 2017-11-27
Primary completion: 2022-11-01
Completion: 2025-07-01

Outcome

Missed primary endpoint

paper Median PFS did not vary significantly by treatment: 4.7 (95% CI, 1.9 to 7.6) and 3.7 (95% CI, 1.6 to 6.7) months PMID 39761503 ↗

registry analysis (superiority test); Trastuzumab + Pertuzumab vs Cetuximab + Irinotecan; p = 0.44; NCT03365882 ↗

Publications

Raghav KPS, Guthrie KA, Tan B Jr, Denlinger CS, Fakih M, Overman MJ, Dasari NA, Corum LR, Hicks LG, Patel MS, Esparaz BT, Kazmi SM, Alluri N, Colby S, Gholami S, Gold PJ, Chiorean EG, Kopetz S, Hochster HS, Philip PA. Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With RAS/BRAF Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial. J Clin Oncol. 2025 Apr 10;43(11):1348-1357. doi: 10.1200/JCO-24-01710. Epub 2025 Jan 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Cetuximab	Monoclonal antibody	500 mg/m2	Intravenous
Subject	Irinotecan	Small molecule	180 mg/m2	Intravenous
Subject	Pertuzumab	Monoclonal antibody	420 mg	Intravenous
Subject	Trastuzumab	Monoclonal antibody	6 mg/kg	Intravenous