The design of an ongoing phase 2 study (NCT04412629) evaluating the efficacy and safety of the multitarget tyrosine kinase inhibitor cabozantinib in patients with high-grade neuroendocrine neoplasms (NENs) was presented at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.
High-grade NENs are typically treated with platinum doublet chemotherapy; however, recurrences are inevitable and survival outcomes for patients with metastatic disease are dismal, underscoring the need for effective salvage treatment options. An ongoing hypothesis-generating phase 2 study (NCT04412629) is evaluating the efficacy and safety of the multitarget tyrosine kinase inhibitor cabozantinib in patients with high-grade NENs; the study design of this trial was presented at the 2020 North American Neuroendocrine Tumor Society Annual Symposium.
The eligibility criteria of the trial include patients with histologically confirmed high-grade, poorly differentiated NENs, excluding small-cell lung cancer, whose disease has progressed on first-line therapy; Eastern Cooperative Oncology Group performance status of 0 to 1; and Ki67 of ≥20% or mitotic count of >20 mitoses/high power field. Patients with transformed NENs, NENs of unknown origin, and mixed NENs were also eligible if a high-grade component is established. Eligible patients will receive oral cabozantinib at 60 mg daily on days 1 to 21 of a 21-day cycle.
The primary study end point is overall response rate; the secondary end points are safety, overall survival, and progression-free survival. Correlative studies for genetic and proteomic analysis will be performed using biopsy tissue acquired prior to cycle 2, as well as circulating tumor DNA from peripheral blood samples on day 1 of each cycle and on day 15 of cycle 1. Genetic analysis includes assessment of standard tumor markers, such as chromogranin, serotonin, urine 5-hydroxyindoleacetic acid, and specific hormones, dependent on the patient and investigator discretion. Whole-exome sequencing with copy number variant estimates of the initial biopsy (or optional start of treatment biopsy) will be performed.
A Simon optimal 2-stage design will test the null hypothesis that the true response rate is ≤1% at the type I error rate of 5%. In the first stage, a total of 14 patients are planned for accrual; the study will progress to the second stage if 1 response is achieved in the 14 patients, and 18 additional patients will be recruited. Preliminary evidence for efficacy will be concluded if ≥2 responses are observed in the total 32 patients enrolled.
Source: Trikalinos N, et al. North American Neuroendocrine Tumor Society 2020 Annual Symposium; October 1-3, 2020. Abstract T3.