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.
Post-menopausal women with histologically or cytologically confirmed metastatic or loco-regionally recurrent ER-positive HER2-negative breast cancer before randomization and fulfilling all of the inclusion criteria and none of the exclusion criteria will be included. After the screening visit and confirmation of eligibility, patients will be randomly assigned in a 1:1:1:1 ratio to receive 1 of the following 4 treatments, consisting of 4-week treatment cycles until disease progression (assessed by the Investigator as defined by Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1): * AZD9833 (Dose A) * AZD9833 (Dose B) * AZD9833 (Dose C) * Fulvestrant (500 mg) During the treatment period, patients will have scheduled visits until treatment discontinuation. After the end of treatment, patients will attend 2 safety follow-up visits (at the time of treatment discontinuation and 28 days later) and will continue to be followed for survival. As of December 2020, the Sponsor stopped enrolment to Dose C.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
240
Dosage formulation: AZD9833 tablets will be administered orally.
Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.
Progression-free Survival (PFS)
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.
Time frame: 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)
Objective Response Rate (ORR)
ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Adjusted response rate was presented in this analysis. 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.
Time frame: From screening until disease progression (up to data cut-off of 29 months)
Duration of Response (DoR)
DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Time frame: From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)
Percentage Change in Tumour Size at 16 Weeks
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Research Site
Birmingham, Alabama, United States
Research Site
Long Beach, California, United States
Research Site
Fort Myers, Florida, United States
Research Site
St. Petersburg, Florida, United States
Research Site
Lincoln, Nebraska, United States
Research Site
Canton, Ohio, United States
Research Site
Chattanooga, Tennessee, United States
Research Site
Nashville, Tennessee, United States
Research Site
Eagle River, Wisconsin, United States
Research Site
Brasschaat, Belgium
...and 76 more locations
The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.
Time frame: At Week 16
Overall Survival (OS)
The OS was defined as the time from randomisation to death due to any cause.
Time frame: From the date of randomisation until death (up to data cut-off of 29 months)
Clinical Benefit Rate at 24 Weeks (CBR24)
Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization. Adjusted response rate was presented in this analysis. 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.
Time frame: At Week 24
Plasma Concentrations of AZD9833
The plasma concentrations of AZD9833 at steady state were evaluated.
Time frame: Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)
Percent Change From Baseline in ER and PgR Expression and Ki67 Labelling Index
The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.
Time frame: From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)
Changes From Baseline in Health Related Quality of Life (HRQoL)
To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.
Time frame: From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)