DETECT IV - A Study in Patients With HER2-negative Metastatic Breast Cancer and Persisting HER2-negative Circulating Tumor Cells (CTCs).

Prior treatment

• Treatment with other investigational agents of any type or anticancer therapy during the trial, within 2 weeks prior to the start of treatment.
• Adverse events due to prior anticancer therapy which are \> Grade 1 (NCI CTCAE) and therapeutically relevant at time of treatment start.
• Concurrent disease or condition that might interfere with adequate assessment or evaluation of study data, or any medical disorder that would make the patient's participation unreasonably hazardous.
• Disease or condition, which might restrain the ability to take or resorb oral medication. This includes malabsorption syndrome, requirement for intrave-nous (IV) alimentation, prior surgical procedures af-fecting absorption (for example resection of small bowel or stomach), uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis) and any other diseases significantly affecting gas-trointestinal function as well as inability to swallow and retain oral medication for any other reason.
  • For Eribulin only:

Other illness

• Known HIV infection.
• Current active hepatitis B or C, cliniclally relevant known liver dysfunction, e.g. according to Child Pugh Classifica-tion class B and C, or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gall-stones, liver metastases or stable chronic non-viral liver disease per investigator assessment).
• Other malignant diseases within the last 3 years (apart from carcinoma in situ of the cervix or non-melanoma skin cancer)
• Dementia, altered mental status, or any psychiatric or social condition which would prohibit the understanding or rendering of informed consent or which might interfere with the patient's adherence to the protocol.
• Known hypersensitivity to any of the excipients of ribociclib, everolimus or any of the other given drugs.
• Known hypersensitivity to lecithin (soya) and pea-nuts (ribocilib-cohort)
• History of hypersensitivity reactions attributed to eribulin.

Lab values

• Severe Congenital long QT syndrome.

Other

• In General for both study cohorts:
• Life expectancy \< 3 months.
• Male gender.
  • For Everolimus/Ribociclib only:
• Pre-existing neuropathy grade 3 or higher.
• Pregnancy or nursing.

• Both cohorts:
• Indication for an endocrine therapy (Histological confirmation of estrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+) breast cancer).
• Up to two lines of previous cytostatic treatment for MBC.
• Any endocrine therapy in the history is allowed.
• Disease progression following prior treatment with endocrine therapy (endocrine therapy does not have to be the last therapy before inclusion in the trial).
• Postmenopausal women. The investigator must confirm postmenopausal status Postmenopausal status is defined either by
  • Age ≥ 55 years and one year or more of amenorrhea
• \- Age \< 55 years and one year or more of amenorrhea and postmenopausal levels of FSH and LH
• \- Prior hysterectomy and has postmenopausal levels of FSH and LH
• \- Surgical menopause with bilateral oophorectomy
• Everolimus cohort:
• Cholesterol ≤ 2.0 × ULN
• Ribociclib cohort:
• Standard 12-lead ECG values assessed by the local laboratory:
• \- QTcF interval at screening \< 450 msec (using Fridericia's correction)
• \- Resting heart rate 50-90 bpm
• INR ≤ 1,5 (ribocilclib cohort)
• Patients must have the following laboratory values within normal limits or corrected to within normal lim-its with supplemets before the first dose of study medication:
• -Sodium
• -Potassium
• -Total calcium
  • For Eribulin only:
• Either hormone-receptor negative MBC or hormone-receptor positive MBC with indication for chemotherapy
• Up to three previous chemotherapy treatment lines for metastatic disease
• In case of patients of child bearing potential:
  • Negative pregnancy test (minimum sensitivity 25IU/L or equivalent units of HCG) within 7 days prior to recruitment
  • Contraception by means of a reliable method (i.e. non-hormonal contraception, IUD, a dou-ble barrier method, vasectomy of the sexual partner, complete sexual abstinence). Patient must consent in maintaining such contracep-tion until 3 months after completion of study treatment