Tucatinib With Brain and/or Spinal XRT in Patients With HER2+ Metastatic Breast Cancer and LMD

• Status: Recruiting
• Trial end date: 2028-10-05
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Biocon Biologics; Seagen Inc.
• Treatments: Capecitabine; Trastuzumab; Tucatinib

Criteria

Inclusion Criteria: Phase 1

1. Men or women with HER2+ metastatic breast cancer.

2. Evidence of LMD in the brain and/or spine

3. Age 18+ at time of consent;

4. ECOG ≤ 2;

5. If applicable, the last dose of prior chemotherapy, immunotherapy, endocrine therapy therapy must have been completed 14 days prior to study enrollment.

6. More than 14 days or 5 half-lives from the last dose of any experimental agent is required, whichever is greater;

7. 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.

Phase 2: Inclusion Criteria

1. 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;

2. Adequate hematologic, liver, and renal function within 2 weeks prior to phase 2 enrollment, as follows:

1. Hemoglobin ≥ 9 g/dL

2. ANC ≥ 1 x109/L

3. Platelets ≥ 100 x109/L

4. Total bilirubin ≤ 1.5 X upper limit of normal (ULN)

5. AST and ALT ≤ 2.5X ULN

6. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN

7. Creatinine clearance (CrCL) ≥ 50 mL/min

Exclusion Criteria: Phase 1

1. Prior WBRT for brain metastases

2. Prior therapy specifically directed at LMD

3. Inability to comply with MRI-based surveillance of CNS disease.

4. Inability to swallow pills or any significant gastrointestinal diseases such as inflammatory bowel disease.

5. Presently known dihydropyrimidine dehydrogenase deficiency;

6. Diagnosed with Hereditary fructose intolerance;

7. Diagnosed with Gilbert's disease;

8. Prior history of other cancer with evidence of disease within the last 5 years;

9. Prior use of tucatinib at any time prior to enrollment.

Phase 2:

1. Currently pregnant or breastfeeding;

2. 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

3. Myocardial infarction or unstable angina within 6 months prior to the first dose of systemic therapy.

4. Blood product transfusions in order to meet eligibility criteria