Spots Global Cancer Trial Database for Evaluation of Trastuzumab in Combination With Lapatinib or Pertuzumab in Combination With Trastuzumab-Emtansine to Treat Patients With HER2-positive Metastatic Colorectal Cancer

Study Description

Brief Summary: This is a Phase II multi-center 2-sequential cohorts trial, designed to assess the objective response rate of two anti HER2 combination in advanced disease CRC patients harbouring an amplified HER2 tumor assessed according to HERACLES Diagnostic Criteria by FISH/SISH. Cohort A: monoclonal antibody trastuzumab, used in combination with the small molecule tyrosine kinase inhibitor lapatinib. Cohort B, monoclonal antibody pertuzumab, used in combination with the antibody drug conjugate trastuzumab-emtansine. Please note that cohort A accrual has been closed and endpoint already reached.

Detailed Description: Investigators identified HER2 amplification as a potential onco-driver and marker of de novo resistance to anti-EGFR therapy in mCRC patients for which other known genetic alterations conferring resistance to anti EGFR antibodies were excluded. Exploiting direct transfer xenografts of mCRC surgical samples in mice (xenopatients), investigators conducted a multi-arm study in HER2-amplified xenopatients showing that combinations of the dual EGFR/HER2 inhibitor lapatinib and the anti-HER2 moAb trastuzumab induced long-lasting tumor regressions, while monotherapy with lapatinib led to stabilization and monotherapy with trastuzumab was ineffective. On these findings investigators designed the HERACLES trial. HERACLES is an open-label Phase II, 2-sequential cohorts trial, assessing the response rate (ORR) of Trastuzumab combined Lapatinib (Cohort A) or Pertuzumab combined with trastuzumab-emtansine (Cohort B), in metastatic colorectal patients harboring an amplified HER2 tumors . HER2 positivity is centrally established by immunohistochemistry (IHC) and Silver In Situ Hybridization (SISH). To be HER2 eligible the original tumor, or the biopsied metastasis (whichever is last available), must be IHC 3+ or 2+ in more than 50% of cells, confirmed by SISH or FISH with a HER2:CEP17 ratio ≥ 2.0. For IHC a positive staining (3+) is defined as an intense membrane staining which can be circumferential, basolateral, or lateral of the tumor cells.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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