A Phase 1b/2 Trial Evaluating Safety and Efficacy of CAPecitabine in Combination With Ni-rapaRIb in HER2-negative Advanced Breast canCEr

1. Measurable or non-measurable disease, per RECIST v. 1.1, must be present outside the CNS

2. No history of intracranial haemorrhage or spinal cord haemorrhage

3. Metastases are limited to the cerebellum or the supratentorial region (i.e., no metasta-ses to the midbrain, pons, medulla, or spinal cord).

4. There is no evidence of interim progression between completion of CNS-directed ther-apy and the screening brain scan.

5. The patient has not received stereotactic radiotherapy within 7 days prior to initiation of study treatment or whole-brain radiotherapy within 14 days prior to initiation of study treatment.

6. The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.

Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.

1. Prior treatment with a PARP inhibitor and capecitabine for metastatic disease, (Patients treat-ed with these drugs in the adjuvant setting are allowed to participate if they experienced 2 years from end of treatment and metastatic relapse)

2. Patient has a Dihydropyrimidine dehydrogenase deficiency (DPD)

3. Patients must not have received anticancer chemotherapy, targeted therapy within 2 weeks prior of the study. Endocrine therapy must have been discontinued 7 or more days before Cycle 1 Day 1. Participant must not have had investigational therapy administered within 4 weeks or with-in a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.

4. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. Biphosphonates and denosumab are allowed.

5. Major surgery within 3 weeks prior to registration. Patients must have recovered from earlier major surgery before registration.

6. Persistent toxicities (≥NCI-CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and NCI-CTCAE grade 2 peripheral neuropathy.

7. Immunocompromised patients (e.g. HIV) for part I and but patients with well controlled HIV could be included in part II (negative viral load)

8. Patients considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection, symptomatic congestive heart fail-ure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or Posterior Reversible Encephalopathy Syn-drome (PRES).

9. Mean resting QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 consecutive electrocardiograms using Fridericia's Correction.

10. Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative colitis).

11. Patients unable to swallow orally administered medication, patients with gastrointestinal dis-orders likely to interfere with absorption of niraparib, and patients with long-term oral anticoagu-lant therapy.

12. Pregnant or breast-feeding women. Participant must agree to not breastfeed during the study and for 30 days after the last dose of study treatment

13. Known hypersensitivity to niraparib or capecitabine or any of the excipients of the products

14. Patient is currently receiving or has received sorivudine or brivudine within 4 weeks prior to starting capecitabine

15. Patient has received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy

16. Patient has received colony-stimulating factors (e.g. granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) ≤ 4 weeks prior to initiating protocol therapy

17. Patient has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks

18. Patient has any known history of myelodysplastic syndrome (MDS) or acute myeloid leuke-mia (AML)

19. Patient has a diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating study therapy with the following exceptions: basal or squamous cell carcinoma of the skin, cervical cancer in situ that has been definitively treated, adequately treated nonmelanoma skin cancer, ductal carcinoma in situ (DCIS) of the breast.

20. Patient has known active hepatitis B (e.g. hepatitis B surface antigen (HBsAg\] reaction) or hepatitis C (e.g. hepatitis C virus \[HCV\] ribonucleic acid \[qualitative\] is detected)

21. Participants have received live vaccine within 30 days of planned start of study registration. 22. Participants have current active pneumonitis or any history of pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study.

What this study is about