Trial Outcomes & Findings for T-DM1 Alone Versus T-DM1 and Metronomic Temozolomide in Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases Following Stereotactic Radiosurgery (NCT NCT03190967)

The phase II portion was never started as we could no longer get the drug from the manufacturer.

T-DM1 Alone Versus T-DM1 and Metronomic Temozolomide in Secondary Prevention of HER2-Positive Breast Cancer Brain Metastases Following Stereotactic Radiosurgery

Maximum tolerated dose of TMZ when used in combination with T-DM1. MTD is defined as the dose level at which 0 or 1 participant in 6 has a dose limiting toxicity (DLT). A DLT is defined as grade 3 or higher non-hematologic adverse events excluding grade 3 hypertension controlled with anti-hypertensive therapy; or grade 3 asymptomatic electrolytes imbalance; grade 3 endocrinopathy; grade 3 asymptomatic increase in aspartate aminotransferase or alanine aminotransferase; and transient (lasting less than \<48 hours) nausea, emesis, or diarrhea if corrected with conservative measures within 24-48 hours. A hematologic grade 4 neutropenia of ≥ 7 days duration, grade ≥ 3 thrombocytopenia, and all other grade 4 hematologic toxicities excluding grade 4 lymphopenia, or leukopenia in the absence of grade 3 or higher neutropenia. Grade 3 is severe. Grade 4 is life-threatening.

Median time to progression. Progression was assessed using the Response Assessment in Neuro-oncology Brain Metastases (RANO-BM) Criteria for evaluation of brain lesions, and the Response Evaluation Criteria in Solid Tumors (RECIST) for systemic evaluation. Progression is a 25% increase in the sum of products of all measurable lesions observed over baseline if no decrease. Or appearance of new lesions, or failure to return for evaluation due to death or deteriorating condition.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening.

Number of participants with DLTs at each dose level 30 days after treatment. A DLT is defined as grade 3 or higher non-hematologic adverse events excluding grade 3 hypertension controlled with anti-hypertensive therapy; or grade 3 asymptomatic electrolytes imbalance; grade 3 endocrinopathy; grade 3 asymptomatic increase in aspartate aminotransferase or alanine aminotransferase; and transient (lasting less than \<48 hours) nausea, emesis, or diarrhea if corrected with conservative measures within 24-48 hours. A hematologic grade 4 neutropenia of ≥ 7 days duration, grade ≥ 3 thrombocytopenia, and all other grade 4 hematologic toxicities excluding grade 4 lymphopenia, or leukopenia in the absence of grade 3 or higher neutropenia. Grade 3 is severe. Grade 4 is life-threatening.

Time to whole brain irradiation compared between the two arms and Kaplan-Meier curves constructed with a two-tailed log-rank test used to compare the arms.

Median amount of time participants survives after therapy. Survival compared between the two arms and Kaplan-Meier curves constructed with a two-tailed log-rank test used to compare the arms.

TTP is the time between the first day of treatment to the day of disease progression. Progression was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 25% increase in the sum of products of all measurable lesions over smallest sum observed, clear worsening of any evaluable disease, appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition.

Median amount of time participants survives after therapy. Survival compared between the two arms and Kaplan-Meier curves constructed with a two-tailed log-rank test used to compare the arms.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.