SFX-01 in the Treatment and Evaluation of Metastatic Breast Cancer

NCT02970682 | Completed Phase 2

• 1 other identifier: EVG001BC
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 10

Brief Summary

This is a Phase 2 study to demonstrate the safety and efficacy of SFX-01 when used in combination with aromatase inhibitors (AIs), tamoxifen and fulvestrant. Patients will be enrolled into one of three study arms (SFX-01 in combination with AI, tamoxifen or fulvestrant) based on their current therapy.

Conditions

Breast Neoplasm

Outcome Measures

Primary Outcomes (2)

• Treatment-Emergent Adverse Events [Safety and Tolerability])

  To determine the safety and tolerability of SFX-01 in combination with AI, tamoxifen and fulvestrant

  28 weeks

• Clinical benefit rate

  To determine clinical benefit rate (CBR) (CR+PR+SD) at 24 weeks using RECIST v1.1

  24 weeks

Secondary Outcomes (7)

• Objective Response rate

  24 Weeks

• Time To Response

  24 weeks

• Time to Progression

  24 Weeks

• Progression Free Survival

  24 Weeks

• Overall Survival

  24 Weeks

Study Arms (3)

Aromatase Inhibitor

EXPERIMENTAL

SFX-01 with Aromatase Inhibitor SFX-01 when used in combination with aromatase inhibitors. All patients will continue to receive their AI and, at the start of the study (D1), patients will take SFX-01, which is provided as 300 mg capsules, one to be taken twice daily, 12 hours apart, after food (preferably within 2 hours).

Drug: SFX-01; Drug: Aromatase Inhibitors

Fulvestrant

EXPERIMENTAL

SFX-01 with Fulvestrant SFX-01 when used in combination with fulvestrant. All patients will continue to receive fulvestrant 500 mg IM in 28 day cycles. As patients will already have been taking this, a repeat loading dose is not necessary. Commencing on study D1 patients will take SFX-01, which is provided as 300 mg capsules, one to be taken twice daily, 12 hours apart, after food (preferably within 2 hours).

Drug: SFX-01; Drug: Fulvestrant

Tamoxifen

EXPERIMENTAL

SFX-01 with Tamoxifen SFX-01 when used in combination with tamoxifen All patients will continue to receive tamoxifen and, at the start of the study (D1), patients will take SFX-01, which is provided as 300 mg capsules, one to be taken twice daily, 12 hours apart after food (preferably within 2 hours).

Drug: SFX-01; Drug: Tamoxifen

Interventions

SFX-01 DRUG

Stabilised Sulforaphane

Also known as: Sulforadex

Aromatase Inhibitor; Fulvestrant; Tamoxifen

Fulvestrant DRUG

Fulvestrant

Fulvestrant

Tamoxifen DRUG

Tamoxifen

Tamoxifen

Aromatase Inhibitors DRUG

Aromatase Inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• 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;
• 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;
• Patients with clinical or histological confirmation of metastatic or locally advanced disease not amenable to curative surgical resection;
• 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);
• Patients must have an anticipated life expectancy of at least 12 weeks;
• 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);
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2;
• Must currently be on either a third generation aromatase inhibitor, tamoxifen or fulvestrant and have a documented evidence of progressive disease after:

You may not qualify if:

• Rapidly progressive visceral disease not suitable for further endocrine therapy;
• Currently on chemotherapy or any other combination treatment for their MBC other than AI, tamoxifen or fulvestrant;
• Radiotherapy less than 2 weeks prior to study entry;
• Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment;
• 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;
• 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;
• 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;
• An existing serious disease, illness, or condition that will prevent participation or compliance with study procedures;
• Patients with unresolved or unstable serious toxicity from prior administration of another investigational drug and/or prior cancer treatment;
• 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.
• 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);
• Females who are pregnant, wishing to become pregnant or breast feeding.

Sponsors & Collaborators

• Evgen Pharma: lead
• Premier Research: collaborator

Study Sites (10)

Grand Hopital de Charleroi, Service D'Oncologie-Hematologie

Charleroi, 6000, Belgium

Location

Saint-Luc hospital, Brussels

Woluwe-Saint-Lambert, 1200, Belgium

Location

ICO René Gauducheau, St Herblain

Nantes, Loire Atlantique, 44805, France

Location

Granollers Hospital, Granollers,

Barcelona, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 100, Spain

Location

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

University Hospitals Birmingham NHS Foundation

Birmingham, B15 2TH, United Kingdom

Location

Royal Bournemouth & Christchurch Hospitals NHS

Bournemouth, BH7 7DW, United Kingdom

Location

Academic unit of Clinical Oncology

Sheffield, S10 2SJ, United Kingdom

Location

Royal Albert & Edward Infirmary

Wigan, WN1 2WN, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; Tamoxifen; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Sacha Howell, MD PhD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 22, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: March 1, 2019
• Last Updated: July 12, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); GB (5); ES (2); BE (2)