Clinical trial NCT04214288: 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
Official title: SERENA-2: A Randomised, Open-Label, Parallel-Group, Multicentre Phase 2 Study Comparing the Efficacy and Safety of Oral AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced ER-Positive HER2-Negative Breast Cancer
Keywords: Open-Label
Parallel-Group
Fulvestrant
ER-Positive HER2-Negative Breast Cancer
Metastatic
AZD9833
Oral SERD
Camizestrant
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-01-02
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Eligibility criteria: 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 outcomes:
measure: Progression-free Survival (PFS)
timeFrame: 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)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From screening until disease progression (up to data cut-off of 29 months)
measure: Duration of Response (DoR)
timeFrame: From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)
measure: Percentage Change in Tumour Size at 16 Weeks
timeFrame: At Week 16
measure: Overall Survival (OS)
timeFrame: From the date of randomisation until death (up to data cut-off of 29 months)
measure: Clinical Benefit Rate at 24 Weeks (CBR24)
timeFrame: At Week 24
measure: Plasma Concentrations of AZD9833
timeFrame: 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)
measure: Percent Change From Baseline in ER and PgR Expression and Ki67 Labelling Index
timeFrame: From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)
measure: Changes From Baseline in Health Related Quality of Life (HRQoL)
timeFrame: From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)
Other outcomes:
measure: Number of Patients With Adverse Events
timeFrame: From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Long Beach
country: United States
facility: Research Site
state: California
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Eagle River
country: United States
facility: Research Site
state: Wisconsin
city: Brasschaat
country: Belgium
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Haine-Saint-Paul
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Libramont-Chevigny
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Paris
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Batumi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Tbilisi
country: Georgia
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Düsseldorf
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Kecskemét
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Pécs
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catanzaro
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Messina
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Umbria
country: Italy
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Piła
country: Poland
facility: Research Site
city: Rzeszów
country: Poland
facility: Research Site
city: Skorzewo
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Almada
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Loures
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Kazan
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Kursk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Cherkasy
country: Ukraine
facility: Research Site
city: Chernivtsі
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: M. Kyiv
country: Ukraine
facility: Research Site
city: S. Khodosivka
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Derby
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
Study officials:
References: