Clinical trial NCT02376985 (phase 3, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: everolimus
SMILES: [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC
Eligibility criteria:

        Inclusion Criteria:

          1. Female patients with a histological diagnosis of breast cancer (regardless of
             histological subtype of breast cancer).

          2. Diagnosis of metastatic or recurrent breast cancer satisfies either of the below.

               1. Distant metastasis present that is inoperable at time of first examination (Stage
                  IV, 3.1 Clinical stage classification)

               2. Progression of distant metastasis or recurrence of breast cancer after treatment
                  (after surgery and after treatments prior to and after surgery)

          3. Histologically confirmed diagnosis of ER-positive breast cancer

          4. Postmenopause

          5. Any of the below conditions indicating resistance to aromatase inhibitor therapy. The
             aromatase inhibitor therapy need not be the most recent therapy.

               1. Recurrence during ongoing adjuvant therapy with an aromatase inhibitor, or
                  recurrence within 12 months after adjuvant therapy with an aromatase inhibitor

               2. Progression during ongoing aromatase inhibitor therapy for advanced breast
                  cancer, or progression within 1 month after ending aromatase inhibitor therapy

          6. Any number of chemotherapy (anti-neoplastic drugs) are allowed since diagnosis of
             metastatic or recurrent breast cancer

          7. Aged ≥20 years

          8. PS of 0-1. (ECOG scale).

          9. Previous treatment (including adjuvant therapy) satisfies all the conditions below.

               1. Hormone therapy: At least 7 days have elapsed from the last administration of
                  hormonal therapy.

               2. Radiotherapy: At least 14 days have elapsed from the last irradiation.

         10. Organ function (within 4 weeks before enrollment) satisfies all the conditions below.

               1. Neutrophil count (band cells + segmented cells) of ≥1,500/mm3, or white blood
                  cell count of ≥3,000/mm3

               2. Platelet count of ≥100,000/mm3

               3. Total bilirubin of ≤2.5 × ULN

               4. AST (GOT) and ALT (GPT) of ≤2.5 × ULN

               5. Serum creatinine of ≤1.5 × ULN

         11. Cardiac function satisfies either of the below.

               1. No cardiac disorder: No fatigue, palpitation, shortness of breath, or anginal
                  pain during everyday activities as confirmed by interview.

               2. Has a cardiac disorder that does not limit movement, patient is confirmed to
                  experience no fatigue, palpitation, shortness of breath, or anginal pain during
                  everyday activities, and this health status is deemed to be maintained during
                  treatment.

         12. Informed consent is obtainable from the subject herself in documented form using the
             Consent Form.

        Exclusion Criteria:

          1. Edentulous jaw (in both upper and lower jaws)

          2. Occurrence of oral mucositis within 1 month prior to randomization

          3. Chemotherapy used within 1 month prior to randomization

          4. Exemestane monotherapy (this exclusion criterion is not met if ≥3 months has elapsed
             since the last exemestane treatment) as most recent therapy

          5. Previous mTOR inhibitor treatment (everolimus, etc.)

          6. Interstitial pneumonia or pulmonary fibrosis.

          7. Received drug treatment known to have a strong inhibitory or inductive effect on the
             cytochrome P450 (CYP) 3A isozymes (rifabutin, rifampicin, clarithromycin,
             ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) (See Table 4.1.2.1
             and 4.1.2.2 for lists of prohibited concomitant drugs).

          8. Positive result of HBs antigen, HBc antibody and/or HBs antibody.

          9. HCV infection or a history of HCV infection.

         10. History of hypersensitivity to a protocol treatment drug or a vehicle in the drug
             preparation.

         11. Multiple active cancers (homochronous multiple cancers, or heterochronous multiple
             cancers with a cancer-free period of less than 5 years prior to randomization).

             Carcinoma in situ deemed to be cured by local treatment (lesions that are
             intraepithelial carcinoma or mucosal cancer) is not included as an active multiple
             cancer.

         12. Overexpression of HER2 (Her2/neu, Erb B2), and the condition is considered to be
             indicated for trastuzumab (herceptin®) treatment (when the state of HER2 expression is
             unknown, the patient is not excluded, but is treated as eligible).

             In other words, patients that satisfy any of the below conditions will be excluded.

             At either the primary or the metastatic lesion:

               1. Strongly positive, "3+" by HER2 IHC.

               2. Positive "+" by FISH

         13. Brain metastasis that requires treatment for intracranial hypertension or emergency
             irradiation of the brain.

         14. Extensive liver metastasis, or lymphangitic lung metastasis with accompanying dyspnea.

         15. Pleural effusion, ascites, or pericardial effusion that requires emergency treatment.

         16. Concurrent and active infectious disease.

         17. With uncontrolled diabetes mellitus or currently receiving insulin therapy.

         18. Difficulty to participate in this study due to mental illness or psychiatric symptoms.

         19. With another reasons recognized as inadequate to participate in this study by doctors.