Tucatinib Combined With Trastuzumab and TAS-102 for the Treatment of HER2 Positive Metastatic Colorectal Cancer in Molecularly Selected Patients, 3T Study

Stage IV Colorectal Cancer AJCC v8 Clinical Trial

Official title: 3T: A Phase II Single Arm Open Label Study of Tucatinib Combined With Trastuzumab and TAS-102 in Molecularly Selected Patients With HER2+ Metastatic Colorectal Cancer

Status Not yet recruiting

Clinical Trial Summary

This phase II trial studies whether tucatinib combined with trastuzumab and TAS-102 works to shrink tumors in patients with HER2 positive colorectal cancer that has spread to other parts of the body (metastatic) and has one of the following gene mutations detected in blood: PIK3CA, KRAS, NRAS, or BRAF V600. Tucatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps stop or slow the spread of tumor cells. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. TAS-102 is a combination of 2 drugs; trifluridine and tipiracil. Trifluridine is in a class of medications called thymidine-based nucleoside analogues. It works by stopping the growth of tumor cells. Tipiracil is in a class of medications called thymidine phosphorylase inhibitors. It works by slowing the breakdown of trifluridine by the body. Giving tucatinib, trastuzumab, and TAS-102 together may work better than usual treatment for metastatic colorectal cancer.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the 2-month progression free survival (PFS) rate of tucatinib, trastuzumab, and trifluridine and tipiracil hydrochloride (TAS-102) in patients with HER2 amplified and PIK3CA, RAS, and/or BRAF mutated metastatic colorectal cancer (CRC).

SECONDARY OBJECTIVES:

I. To assess the clinical benefit rate (CBR) (stable disease [SD] for >= 4 months, or best response of complete response [CR] or partial response [PR]) of tucatinib, trastuzumab, and TAS-102 in patients with HER2 amplified and PIK3CA, RAS, and/or BRAF mutated metastatic CRC.

II. To assess the objective response rate (ORR) of tucatinib, trastuzumab, and TAS-102 in patients with HER2 amplified and PIK3CA, RAS, and/or BRAF mutated metastatic CRC.

III. To assess the overall survival (OS) of tucatinib, trastuzumab, and TAS-102 in patients with HER2 amplified and PIK3CA, RAS, and/or BRAF mutated metastatic CRC.

IV. To assess the safety and tolerability of tucatinib, trastuzumab, and TAS-102 in patients with HER2 amplified and PIK3CA, RAS, and/or BRAF mutated metastatic CRC.

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess whether the combination of tucatinib, trastuzumab, and TAS-102 eliminates HER2 amplified circulating tumor deoxyribonucleic acid (DNA) (ctDNA) from peripheral blood.

II. To explore the correlation between tissue and blood-based biomarkers and clinical outcomes.

OUTLINE:

Patients receive tucatinib orally (PO) twice daily (BID), trastuzumab intravenously (IV) over 30-90 minutes on days 1 and 15, and TAS-102 PO BID on days 1-5 and 8-12. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days and then every 12 weeks for 4 years after study enrollment. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Colonic Neoplasms
• Colorectal Neoplasms
• Metastatic Colon Adenocarcinoma
• Metastatic Colorectal Adenocarcinoma
• Metastatic Rectal Adenocarcinoma
• Stage IV Colon Cancer AJCC v8
• Stage IV Colorectal Cancer AJCC v8
• Stage IV Rectal Cancer AJCC v8

• NCT number: NCT05356897
• Study type: Interventional
• Source: Academic and Community Cancer Research United
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 30, 2023
• Completion date: May 30, 2029