| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Estrogen Receptor (ER) Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Negative Metastatic Breast Cancer Progressing on either an Aromatase Inhibitor (AI) or Tamoxifen or Fulvestrant |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The main objectives of the trial are:
• To determine the safety and tolerability of SFX-01 in combination with Aromatase Inhibitors, tamoxifen and fulvestrant;
• To determine clinical benefit rate (CBR) (complete response [CR] + partial response [PR] + stable disease [SD]) at 24 weeks using RECIST v1.1. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the trial are:
• To determine objective response rate at 24 weeks using RECIST v1.1;
• To determine time to response;
• To determine time to progression (TTP);
• To determine progression free survival (PFS) at 24 weeks;
• To determine overall survival (OS) at 24 weeks;
• To determine clinical benefit by measuring duration of response compared to duration of response to prior Endocrine Therapy;
• To determine time to next treatment.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The principal inclusion criteria are:
1. Male or female patients 18 years or older (the patient must be within the legal age limit to give informed consent in the jurisdiction the study is taking place in);
2. Patients with histologically confirmed estrogen receptor positive (ER+) breast cancer. Estrogen receptor is considered positive if a percentage score of ≥10% of tumour cells stain positive for ER.;
3. Histological confirmation of Human Epidermal Growth Factor Receptor 2 (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 1 site of measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) ≥10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI) scan (malignant lymph nodes should be ≥15 mm 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 nonmeasurable);
6. Patients must have an anticipated life expectancy of at least 12 weeks;
7. Adequate bone marrow, renal and hepatic function defined as follows:
o Haemoglobin > 9 g/dL;
o Absolute neutrophil count > 1.0 x 109/L;
o Platelets > 100 x 109/L;
o Total bilirubin within normal limits, except those with Gilbert’s syndrome for whom this must be <2.5 x ULN;
o AST(SGOT) or ALT(SGPT) < 2.5 x ULN;
o Calculated creatinine clearance > 30 ml/min;
8. Eastern Cooperative Oncology Group (ECOG) performance status < 2;
9. Must currently be on either a third generation Al, tamoxifen or fulvestrant and have a documented evidence of progressive disease after the following:
(a) taking endocrine therapy (ET) as adjuvant therapy for >2 years or
(b) achieving a best response of stable disease (for at least 6 months) or an objective response of complete response (CR) or partial response (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 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 1 prior line of chemotherapy 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 both the initial Screening Visit and at Baseline (Day 1) of the study. |
|
| E.4 | Principal exclusion criteria |
the principal exclusion criteria are:
1. Rapidly progressive visceral disease not suitable for further endocrine therapy;
2. Currently on chemotherapy for their metastatic breast cancer (MBC) even if this is in combination with 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 > 6 As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active infection with hepatitis B, hepatitis C and human immunodeficiency (HIV) viruses. Screening for chronic conditions is not required.;
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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints of the study are:
Safety and tolerability of SFX-01 in combination with aromatase inhibitors, tamoxifen or fulvestrant as assessed by adverse events and requirement for concomitant medications
Efficacy endpoints of clinical benefit rate at 24 weeks assessed by percentage of patients with complete and partial responses and stable disease |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety will be assessed throughout the study until 30 days after the study medication or until any residual adverse events are resolved or have a final outcome
Efficacy endpoint will be assessed every 6 weeks via a computed tomography scan |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints are time to event endpoints of objective response, time to response, time to progression, progression free survival at 24 weeks, overall survival at 24 weeks, measure of clinical benefit and time to next treatment
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| All secondary endpoints will be evaluated using computed tomography scans every 6 weeks |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
There will be exploratory analysis:
• To identify populations that are more or less likely to respond to SFX-01 based on pharmacogenomics and tumour tissue or whole blood biomarker analyses;
• To evaluate serum samples for proteomics;
• To evaluate PK levels of SFX-01, AI, tamoxifen and fulvestrant.
|
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| Czech Republic |
| France |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the trial is defined as last patient last visit |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
