Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Ado-Trastuzumab Emtansine

Trastuzumab

Pertuzumab

Lapatinib

Adenosine

Maytansine

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Immunoconjugates

Immunologic Factors

Tyrosine

Patients enrolled in Cohort A will receive lapatinib 1000 mg daily per os + trastuzumab 4 mg/kg iv load, followed by 2 mg/kg iv weekly. Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever come first.

Trastuzumab, Lapatinib

Patients enrolled in Cohort B will receive pertuzumab 840 mg iv load, followed by 420 mg iv Q3weeks + trastuzumab-emtansine 3.6 mg/kg iv on day 1 of each subsequent 3 week cycle.

Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever come first.

Pertuzumab, trastuzumab-emtansine

Salvatore Siena, MD

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.

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.

two sequential cohorts: cohort A (lapatinib + trastuzumab); cohort B (pertuzumab + trastuzumab-emtansine).

Evaluation of Trastuzumab in Combination With Lapatinib or Pertuzumab in Combination With Trastuzumab-Emtansine to Treat Patients With HER2-positive Metastatic Colorectal Cancer

Open-Label, Phase II Study of Trastuzumab in Combination With Lapatinib (Cohort A) or Pertuzumab in Combination With Trastuzumab-emtansine (Cohort B) in Patients With HER2-positive Metastatic Colorectal Cancer: the HERACLES (HER2 Amplification for Colo-rectaL Cancer Enhanced Stratification)Trial

Fondazione del Piemonte per l'Oncologia

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Joaquin Gávila, MD

A retrospective, observational, not EPA, multicenter study to evaluate the Clinical Benefit of Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib between January 2005 and December 2011

Clinical Benefit of the Treatment With Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib

Observational, Retrospective and Multicenter Study to Evaluate the Clinical Benefit of Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib

clinical benefit rate (CBR): defined as the percentage of patients who achieved an objective response (CR or PR) or tumor stabilization for at least 24 weeks or more during the period of treatment with the combination TL.

This variable will be assessed by RECIST v 1.1

The progression will be evaluated by RECIST v 1.1.

clinical benefit: defined as reaching a (complete or partial) objective response or stabilization of tumor for more than 24 weeks

Adverse reactions observed during treatment of the combination TL, measured with scale CTCAE v.4

MedSIR

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evaluation of Trastuzumab in Combination With Lapatinib or Pertuzumab in Combination With Trastuzumab-Emtansine to Treat Patients With HER2-positive Metastatic Colorectal Cancer	NCT03225937	Metastatic Colo...	Trastuzumab, La... Pertuzumab, tra...	18 Years -	Fondazione del Piemonte per l'Oncologia
Clinical Benefit of the Treatment With Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib	NCT02056080	Breast Neoplasm		18 Years -	MedSIR
Clinical Benefit of the Treatment With Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib	NCT02056080	Breast Neoplasm		18 Years -	MedSIR
Clinical Benefit of the Treatment With Trastuzumab in Combination With Lapatinib in Metastatic Breast Cancer HER2 Positive Patients Who Has Been Previously Treated With Trastuzumab and/or Lapatinib	NCT02056080	Breast Neoplasm		18 Years -	MedSIR
Evaluation of Trastuzumab in Combination With Lapatinib or Pertuzumab in Combination With Trastuzumab-Emtansine to Treat Patients With HER2-positive Metastatic Colorectal Cancer	NCT03225937	Metastatic Colo...	Trastuzumab, La... Pertuzumab, tra...	18 Years -	Fondazione del Piemonte per l'Oncologia

Spots Global Cancer Trial Database for trastuzumab, lapatinib