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

NCT06016387 | Recruiting Phase 2 DMC

• 1 other identifier: CLIMB-LMD
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

HER2-positive Breast Cancer; LMD

Keywords

HER2+; Breast Cancer; Leptomeningeal disease; Tucanitib; CLIMB-LMD; HER2 CLIMB LMD; CLIMB LMD HER2+

Outcome Measures

Primary Outcomes (1)

• Survival status from the start of XRT

  To assess overall survival (OS) in the intention to treat population from the start of XRT.

  From date of baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (7)

• Time to CNS progression from the start of XRT

  From date of baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Safety and tolerability (CTCAE v.5.0)

  From date of baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• Progression free survival from the start of XRT

  From date of baseline until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• CNS specific objective response (RANO-BM)

  Every 6 weeks through study completion, an average of 5 years

• Extracranial objective response (RECIST v1.1)

  Every 6 weeks through study completion, an average of 5 years

Study Arms (1)

Tucatinib, Transtuzumab, Capecitabine

EXPERIMENTAL

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.

Drug: Tucatinib 150 MG; Drug: Trastuzumab; Drug: Capecitabine; Radiation: Brain & Spinal Radiation

Interventions

Tucatinib 150 MG DRUG

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.

Also known as: Tukysa

Tucatinib, Transtuzumab, Capecitabine

Trastuzumab DRUG

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.

Tucatinib, Transtuzumab, Capecitabine

Capecitabine DRUG

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.

Tucatinib, Transtuzumab, Capecitabine

Brain & Spinal Radiation RADIATION

Brain \& Spinal XRT is a treatment for patients with HER2+ metastatic breast cancer and leptomeningeal disease,

Also known as: Brain & Spinal XRT

Tucatinib, Transtuzumab, Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women with HER2+, HER2 mutated and/or HER2-amplified metastatic breast cancer. HER2+ status will be defined in accordance with ASCO-CAP 2018 guidelines, and can be diagnosed at any time prior to enrolment. HER2 mutations and/or HER2-amplifications can be identified in the blood and/or cerebrospinal fluid (CSF) at any time prior to enrolment; testing blood and/or CSF is not part of the study protocol and must be evaluated using a clinically validated test.
• Evidence of LMD\* in the brain and/or spine (either positive cerebral spinal fluid cytology and/or magnetic resonance imaging evidence of LMD). Measurable disease in the central nervous system is not required. \* The diagnosis of LMD can occur at any time prior to enrolment;
• Age 18+ at time of consent;
• ECOG ≤ 2;
• More than 14 days or 5 half-lives from the last dose of any experimental agent is required, whichever is greater;
• All toxicity related to prior cancer therapies must have resolved to ≤ Grade 1 prior to enrollment, except for alopecia; neuropathy, must have resolved to ≤ Grade 2.
• Left ventricular ejection fraction (LVEF) must be within institutional limits of normal as assessed by ECHO or MUGA documented within 2 weeks prior to starting systemic therapy on the study;
• Adequate hematologic, liver, and renal function within 2 weeks prior to phase 2 enrollment, as follows:
• Hemoglobin ≥ 9 g/dL
• ANC ≥ 1 x109/L
• Platelets ≥ 100 x109/L
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
• AST and ALT ≤ 2.5X ULN
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN
• Creatinine clearance (CrCL) ≥ 50 mL/min

You may not qualify if:

• Prior WBRT for brain metastases (prior stereotactic radiosurgery for parenchymal CNS metastases received \<7 days prior to consent );
• Prior therapy specifically directed at LMD, including prior radiotherapy or systemic therapy;
• Inability to comply with MRI-based surveillance of CNS disease;
• Inability to swallow pills or any significant gastrointestinal diseases such as inflammatory bowel disease who suffer from uncontrolled diarrhea (based on the investigator's assessment),, which would preclude adequate absorption of oral medications;
• Diagnosed with Hereditary fructose intolerance;
• Diagnosed with Gilbert's disease;
• Prior history of other cancer (except non melanoma skin, cervical intraepithelial neoplasia) with evidence of disease within the last 5 years;
• Prior use of tucatinib at any time prior to enrollment.
• Hypersensitivity to any of the active substances in tucatinib, trastuzumab, or capecitabine.
• Phase 2:
• Currently pregnant or breastfeeding;
• Use of a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to the first dose of systemic therapy (see Appendix C and D);
• Myocardial infarction or unstable angina within 6 months prior to the first dose of systemic therapy.
• Blood product transfusions in order to meet eligibility criteria

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Biocon Biologics: collaborator
• Pfizer: collaborator

Study Sites (2)

The Ottawa Hospital

Ottawa, Ontario, Canada

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Meningeal Neoplasms

Interventions

tucatinib; Trastuzumab; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

CLIMB-LMD Project Manager

CONTACT

437-247-2617; CLIMB-LMD@sunnybrook.ca

Dr. Katarzyna Jerzak

CONTACT

437-247-2617; katarzyna.jerzak@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 29, 2023
• Study Start: November 25, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): October 5, 2028
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)