Status:
RECRUITING
Tucatinib With Brain and/or Spinal XRT in Patients With HER2+ Metastatic Breast Cancer and LMD
Lead Sponsor:
Sunnybrook Health Sciences Centre
Collaborating Sponsors:
Biocon Biologics
Pfizer
Conditions:
HER2-positive Breast Cancer
LMD
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief 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
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 B...
Eligibility Criteria
Inclusion
- Phase 1
- Men or women with HER2+\* 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;
- 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.
- Phase 2: Inclusion Criteria
- 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
- The last dose of prior therapy must have been completed 14 days prior to study enrollment. Prior chemotherapy, immunotherapy, endocrine therapy, targeted therapy and experimental agents are allowed (including prior use of trastuzumab or other antibody-based therapy). Prior use of capecitabine either alone or in combination with other HER2-targeted therapies (including other tyrosine kinase inhibitors) is permitted;
Exclusion
- Phase 1
- 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;
- Presently known dihydropyrimidine dehydrogenase deficiency;
- 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
Key Trial Info
Start Date :
November 25 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 5 2028
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT06016387
Start Date
November 25 2023
End Date
October 5 2028
Last Update
July 14 2025
Active Locations (2)
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1
The Ottawa Hospital
Ottawa, Ontario, Canada
2
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5