NCT06016387

Tucatinib, Trastuzumab and Capecitabine With Brain and/or Spinal Radiotherapy (XRT) in Patients With HER2+, HER2 Mutated and/or HER2-amplified Metastatic Breast Cancer and Leptomeningeal Disease: A Multi-centre Phase II, Single Arm Feasibility Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Sunnybrook Health Sciences Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The proposed study will evaluate the safety and efficacy of XRT followed by systemic therapy among patients with HER2+, HER2 mutated and/or HER2-amplified metastatic breast cancer and LMD

Detailed description

Breast cancer is the most common cancer among women worldwide, and the second leading cause of brain metastases (BrM). Despite recent treatment advances, the prognosis of patients with breast cancer BrM remains poor, and the prognosis among those with leptomeningeal disease (LMD) is particularly dire with a median survival of only 2-4 months. Patients with HER2+ metastatic breast cancer have a high life-time risk of central nervous system (CNS) metastases, with an approximately 50% lifetime risk. Although the cause of death among patients with breast cancer BrM is challenging to ascertain, approximately 50% of patients with HER2+ BrM are thought to die from central nervous system (CNS) disease involvement. Among patients with LMD specifically, the cause of death is most commonly related to CNS disease. In an analysis of 430 patients (96 of whom had breast cancer) treated for LMD in the National Cancer Database between 2005 and 2014, those patients treated with chemotherapy plus radiotherapy had a longer median overall survival of 5 months (3.5 - 6.5 months) compared to patients treated with XRT or chemotherapy alone. In addition, a majority (n=18/26, 69%) of observational studies irrespective of primary tumor site have shown an "improvement or likely improvement" in survival with the use of XRT for LMD, either alone or in combination with systemic therapy. Hence, this proposed study will evaluate the safety and efficacy of XRT followed by systemic therapy (which is considered standard of care) among patients with HER2+ metastatic breast cancer and LMD. In addition to enrolling patients with established HER2+ metastatic breast cancer, those with HER2 mutations and/or HER2-amplifications in their blood and/or CSF are also eligible to enroll. This is on the basis that the HER2 status is known to "flip" in a relatively high proportion of patients from HER2-negative to HER2-positive at the time that CNS metastases develop51, 52, 53. Given that HER2 status of CNS metastases is not easy to obtain (most patients with CNS metastases do not have surgical resection or biopsy to obtain tissue due to the invasive nature of this surgical approach), patients with fluid samples suggestive of a HER2-driven malignancy (HER2 mutations and/or amplifications) in the blood and/or CSF will be permitted to enrol. Most patients with HER2 amplified tumors would be considered to have HER2-positive disease on tissue samples, but ASCO/CAP guidelines for HER2-positive status only apply to tissue; hence, a separate inclusion criterion for these patients has been established.

Conditions

• HER2-positive Breast Cancer
• LMD

Interventions

Type	Name	Description
DRUG	Tucatinib 150 MG	Tucatinib is a potent, selective, adenosine triphosphate-competitive small-molecule inhibitor of the receptor tyrosine kinase HER2. The molecular formula for tubatinib is C26H24N8O2 and it has a molecular weight of 480.52 g/mol.
DRUG	Trastuzumab	MYL-1401O contains the active substance trastuzumab, which is an IgG1 monoclonal antibody. The molecular size of the intact molecule is around 148 kDa. Each vial of MYL-1401O contains 150 mg of lyophilized proposed active biosimilar substance trastuzumab as well as 3.36 mg L-Histidine Hydrochloride, 2.16 mg L-Histidine, 115.2 mg sorbitol and 33.6 mg PEG-3350 (Macrogol 3350). Sorbitol and PEG-3350 substitute the α- trehalose dehydrate and polysorbate-20, which are used as excipients in the EU-approved and US-licensed Herceptin formulations.
DRUG	Capecitabine	Capecitabine is a tumour-activated antineoplastic agent (antimetabolite). The molecular formula for capecitabine is C15H22FN3O6 and has a molecular weight of 359.35 g/mol.
RADIATION	Brain & Spinal Radiation	Brain \& Spinal XRT is a treatment for patients with HER2+ metastatic breast cancer and leptomeningeal disease,

Timeline

• Start date: 2023-11-25
• Primary completion: 2026-12-31
• Completion: 2028-10-05
• First posted: 2023-08-29
• Last updated: 2026-02-23

Locations

2 sites across 1 country: Canada