A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer
AZD9833: Dosage formulation: AZD9833 tablets will be administered orally.
Fulvestrant: Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.
Study summary
This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria:
* Post-menopausal female patients aged at least 18 years.
* Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of the breast.
* Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.
* Patients must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.
* Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.
* Prior endocrine therapy as follows:
1. Recurrence or progression on at least one line of endocrine therapy
2. No more than 1 line of endocrine therapy for advanced disease
3. No more than 1 line of chemotherapy for advanced disease
4. Prior treatment with CDK4/6 inhibitors is permitted
5. No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies
* Inclusion criterion for the paired tumour biopsy research subgroup:
Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.
Exclusion Criteria:
Intervention with any of the following:
* Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
* Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.
* Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 and sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.
* Drugs that are known to prolong QT and have a known risk of torsades de pointes.
* The following cardiovascular criteria: QTcF \>470 ms, resting heart rate \<45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction \<50%.
* Radiotherapy with a limited field of radiation for palliation within 1 week of dosing, or to \> 30% of bone marrow or a wide field within 4 weeks of dosing.
* Major surgical procedure or significant traumatic injury.
* Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system metastatic disease.
* Inadequate bone marrow reserve or organ function.
* Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833.
* History of hypersensitivity to active or inactive excipients of AZD9833 or fulvestrant.
* Previous randomisation in the present study.
* Women of childbearing potential.
Primary outcome measure(s)
Progression-free Survival (PFS) — From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months) PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Trial sites (85)
Facility
City
Region
Status
Research Site
Birmingham
Alabama
Research Site
Long Beach
California
Research Site
Fort Myers
Florida
Research Site
St. Petersburg
Florida
Research Site
Lincoln
Nebraska
Research Site
Canton
Ohio
Research Site
Chattanooga
Tennessee
Research Site
Nashville
Tennessee
Research Site
Eagle River
Wisconsin
Research Site
Brasschaat
Belgium
Research Site
Charleroi
Belgium
Research Site
Ghent
Belgium
Research Site
Haine-Saint-Paul
Belgium
Research Site
Leuven
Belgium
Research Site
Libramont-Chevigny
Belgium
Research Site
Namur
Belgium
Research Site
Greenfield Park
Quebec
Research Site
Montreal
Quebec
Research Site
Montreal
Quebec
Research Site
Paris
France
Research Site
Vandœuvre-lès-Nancy
France
Research Site
Batumi
Georgia
Research Site
Tbilisi
Georgia
Research Site
Tbilisi
Georgia
Research Site
Tbilisi
Georgia
Research Site
Tbilisi
Georgia
Research Site
Tbilisi
Georgia
Research Site
Berlin
Germany
Research Site
Düsseldorf
Germany
Research Site
Essen
Germany
Research Site
Budapest
Hungary
Research Site
Debrecen
Hungary
Research Site
Kaposvár
Hungary
Research Site
Kecskemét
Hungary
Research Site
Nyíregyháza
Hungary
Research Site
Pécs
Hungary
Research Site
Szeged
Hungary
Research Site
Jerusalem
Israel
Research Site
Jerusalem
Israel
Research Site
Nahariya
Israel
+ 45 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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