Several studies have indicated that determining prevalence and number of circulating tumor cells (CTCs) at various time points during treatment may be an effective tool for assessing treatment efficacy in metastatic breast cancer (MBC). However, even if the prognostic value of CTCs in MBC is well understood, the role of both CTC prevalence and CTC phenotype in predicting treatment response needs further investigation. DETECT IV is a prospective, multicenter, open-label, phase II study in patients with HER2-negative metastatic breast cancer and persisting HER2-negative circulating tumor cells (CTCs). Additional research on CTC dynamics and characteristics will provide a better understanding of the prognostic and predictive value of CTCs and is one step into a more personalized therapy for MBC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
116
Ribociclib/Everolimus in combination with endocrine therapy
University Hospital Ulm -Department of Gynecology
Ulm, Baden-Wurttemberg, Germany
Progression free survival (PFS)
Time interval from randomization until progressive disease (PD) or death from any cause, whichever comes first
Time frame: 8-12 weeks
Overall response rate
Rate of complete (CR) and partial responses (PR) in patients with whom target lesions were defined
Time frame: 8-12 weeks
Disease control rate (DCR)
rate of patients who were assessed as having a PR or a CR or who had stable disease (SD) for at least 6 months
Time frame: 8-12 weeks
Overall survival (OS)
Time from randomization until death of any cause
Time frame: 4 weeks
Dynamic of CTCs
Descriptive statistics of regular CTC counts
Time frame: 8-12 weeks
For Everolimus/Ribociclib cohort only: Levels of pS6
Descriptive statistics of pS6 levels at baseline, at first radiological tumor assessment after about 12 weeks, and at the time of progression
Time frame: 8-12 weeks
For Everolimus/Ribociclib cohort only: Change in the activation of the PI3K/Akt/mTOR-pathway in CTCs
Descriptive statistics of changes in the activation of the PI3K/Akt/mTOR-pathway in CTCs as assessed by longitudinal comparisons (at baseline, after 12 weeks, at time of progression)
Time frame: 8-12 weeks
For Everolimus/Ribociclib cohort only: Estrogen-receptor 1 (ESR-1) mutations in CTCs
Estrogen-receptor 1 (ESR-1) mutations in CTCs at baseline, after 12 weeks and at time of progression
Time frame: 8-12 weeks
For Eribulin cohort only: New metastasis-free survival (nMFS)
New metastasis-free survival (nMFS), defined as time from recruitment to death or progression due to appearance of a new metastasis, whichever comes first. If a patient has not had an event, nMFS is censored at the date of last adequate tumor as-sessment
Time frame: 8-12 weeks
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