Clinical trial NCT02970682 (phase 2, status: completed)
Conditions: breast neoplasm
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: sfx-01, fulvestrant, tamoxifen, aromatase inhibitors
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Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients 18 years or older (the patient must be the legal age limit to
             give informed consent within the jurisdiction the study is taking place in);

          2. Patients with histologically confirmed estrogen receptor positive (ER+) breast cancer.
             ER is considered positive if a percentage score of ≥10% of tumour cells staining
             positive for ER;

          3. Histological confirmation of HER2 negative breast cancer on primary tumour at
             diagnosis or on biopsy of a metastasis. HER2 negative is defined by the ASCO/CAP
             guidelines;

          4. Patients with clinical or histological confirmation of metastatic or locally advanced
             disease not amenable to curative surgical resection;

          5. Patients must have at least one site of measurable disease, defined as at least one
             lesion that can be accurately measured in at least one dimension (longest diameter to
             be recorded) ≥ 10 mm with spiral CT scan or MRI scan (malignant lymph nodes should be
             ≥15mm to be considered measurable); all sites of disease should be noted and followed
             in accordance with RECIST v1.1. (A lytic or mixed lytic-blastic bone lesion with a
             soft tissue component assessed on CT/MRI can be measurable if the minimum size
             criteria are met. Blastic bone lesions and bone lesions assessed on bone scan,
             positron emission therapy (PET) or plain films are non-measurable);

          6. Patients must have an anticipated life expectancy of at least 12 weeks;

          7. Adequate bone marrow, renal and hepatic function defined as:

               -  Haemoglobin > 9 g/dL;

               -  Absolute neutrophil count > 1.0 x 109/L;

               -  Platelets > 100 x 109/L;

               -  Total bilirubin within normal limits, except those with Gilberts syndrome for
                  whom this must be <2.5 x ULN;

               -  AST(SGOT) or ALT(SGPT) < 2.5 x ULN;

               -  Calculated creatinine clearance > 30 ml/min (Appendix 2);

          8. Eastern Cooperative Oncology Group (ECOG) performance status < 2;

          9. Must currently be on either a third generation aromatase inhibitor, tamoxifen or
             fulvestrant and have a documented evidence of progressive disease after:

               1. taking ET as adjuvant therapy for >2 years or

               2. achieving a best response of stable disease (for at least 6 months) or an
                  objective response of CR or PR on the current treatment both indicating the
                  development of secondary resistance to current therapy;

         10. Suitable for continuing endocrine therapy according to the treating clinician. The
             window of discontinuation must not exceed 4 weeks.

         11. All patients (or their legally acceptable representatives) must have signed an
             informed consent document indicating that they understand the purpose of and
             procedures required for the study and are willing to participate in the study.

         12. No more than 3 lines of endocrine therapy for metastatic/locally advanced breast
             cancer including the treatment that the patient is receiving at the time of study
             entry. This can include targeted agents alongside endocrine therapy such as, but not
             limited to, everolimus and palbociclib. Ovarian function suppression therapy is not an
             exclusion for females who are premenopausal and on an ET that can be continued
             throughout the study.

         13. No more than one prior line of chemotherapy/targeted therapy for metastatic/locally
             advanced breast cancer.

         14. Patients with adequately controlled hepatitis C or hepatitis B surface antigen.

         15. No residual toxicity > grade 1 from prior antineoplastic therapy with the exception of
             peripheral neuropathy or neuropathic pain which must be stable (as per investigator
             assessment);

         16. Sexually active male and female patients of childbearing potential must agree to use
             an effective method of birth control (e.g., barrier methods with spermicides, oral or
             parenteral contraceptives and/or intrauterine devices) during the entire duration of
             the study and for 6 months after final administration of study drug. Note that
             sterility in female patients must be confirmed in the patients' medical records and be
             defined as any of the following: surgical hysterectomy or bilateral oophorectomy,
             bilateral tubular ligation, natural menopause with last menses >1 year ago; radiation
             induced oophorectomy with last menses >1 year ago; chemotherapy induced menopause with
             1 year interval since last menses; male patients whose female partner(s) is (are)
             pregnant must use a condom from the time of the first administration of SFX-01 until 3
             months following administration of last dose;

         17. Female patients of childbearing potential must have a negative serum or urine
             pregnancy test at day 1 of the study.

        Exclusion Criteria:

          1. Rapidly progressive visceral disease not suitable for further endocrine therapy;

          2. Currently on chemotherapy or any other combination treatment for their MBC other than
             AI, tamoxifen or fulvestrant;

          3. Radiotherapy less than 2 weeks prior to study entry;

          4. Major surgery (excluding placement of vascular access) within 4 weeks before the first
             dose of study treatment;

          5. Spinal cord compression or brain metastases unless treated and radiologically stable
             for > 6weeks post treatment and not requiring steroids for at least 4 weeks prior to
             start of study treatment;

          6. As judged by the Investigator, any evidence of severe or uncontrolled systemic
             diseases, including active infection including hepatitis B, hepatitis C and human
             immunodeficiency virus (HIV). Screening for chronic conditions is not required;

          7. Refractory nausea and vomiting, patients with malabsorption syndrome, diseases
             significantly affecting gastrointestinal function, resection of the stomach or small
             bowel, or difficulty in swallowing and retaining oral medications;

          8. An existing serious disease, illness, or condition that will prevent participation or
             compliance with study procedures;

          9. Patients with unresolved or unstable serious toxicity from prior administration of
             another investigational drug and/or prior cancer treatment;

         10. Diagnosed or treated for a malignancy other than breast cancer within 1 year, or who
             were previously diagnosed with a malignancy other than breast cancer and have any
             radiographic or biochemical marker evidence of malignancy. Patients with completely
             resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ
             malignancy (other than breast) are not excluded.

         11. Concurrent treatment with another investigational agent or participated in another
             investigational trial unless adequate washout period per the investigational drug PK
             has been achieved (usually this is 5 half lives of a product);

         12. Females who are pregnant, wishing to become pregnant or breast feeding.