SERENA-2: A Comparative Study of AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer

Sponsor

AstraZeneca (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04214288

Collaborator

(none)

240

Enrollment

Locations

Arms

37.6

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced ER-Positive HER2-Negative Breast Cancer	Drug: AZD9833 Drug: Fulvestrant	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 22, 2020

Anticipated Primary Completion Date :

Sep 2, 2022

Anticipated Study Completion Date :

Jun 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD9833 Dose A The patients will receive AZD9833 (Dose A).	Drug: AZD9833 Dosage formulation: AZD9833 tablets will be administered orally.
Experimental: AZD9833 Dose B The patients will receive AZD9833 (Dose B).	Drug: AZD9833 Dosage formulation: AZD9833 tablets will be administered orally.
Experimental: AZD9833 Dose C The patients will receive AZD9833 (Dose C).	Drug: AZD9833 Dosage formulation: AZD9833 tablets will be administered orally.
Active Comparator: Fulvestrant 500 mg The patients will receive Fulvestrant (500 mg).	Drug: Fulvestrant Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1 [From date of randomisation to date of objective disease progression or death (up to approximately 3 years)]
Time from randomisation to objective disease progression (as assessed by RECIST) or death.

Secondary Outcome Measures

Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 [From screening until disease progression (up to approximately 3 years)]
The ORR is defined as the percentage of patients with at least 1 Investigator-assessed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression.
Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1 [From screening until disease progression (up to approximately 3 years)]
The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Percentage change in tumour size at 16 weeks [At Week 16]
Percentage change in the sum of longest target lesions diameters at 16 weeks.
Overall survival (OS) [From the date of randomisation until death (up to approximately 3 years)]
The OS is defined as the time from randomisation to death due to any cause.
Clinical benefit rate at 24 weeks (CBR24) [At Week 24]
Percentage of patients with CBR (defined as best objective response of CR, PR or stable disease [SD] at 24 weeks).
Plasma concentrations of AZD9833 and, if appropriate, metabolite(s) [Cycle 1 Day 15 (pre- and post-dose) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)]
To evaluate the pharmacokinetic (PK) profile of AZD9833 in this patient population at steady state.
Percent change from baseline in ER and PgR expression and Ki67 labelling index. [From baseline to Cycle 2 Day 1 (each cycle is 28 days in length).]
The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.
Changes from baseline in Health Related Quality of Life (HRQoL) [From Day 1 until end of treatment and safety follow up (up to approximately 3 years)]
To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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:

Recurrence or progression on at least one line of endocrine therapy
No more than 1 line of endocrine therapy for advanced disease
No more than 1 line of chemotherapy for advanced disease
Prior treatment with CDK4/6 inhibitors is permitted
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35205
2	Research Site	Long Beach	California	United States	90806
3	Research Site	Fort Myers	Florida	United States	33901
4	Research Site	Saint Petersburg	Florida	United States	33705
5	Research Site	Lincoln	Nebraska	United States	68506
6	Research Site	Canton	Ohio	United States	44710
7	Research Site	Chattanooga	Tennessee	United States	37404
8	Research Site	Nashville	Tennessee	United States	37203
9	Research Site	Eagle River	Wisconsin	United States	54521
10	Research Site	Brasschaat		Belgium	2930
11	Research Site	Charleroi		Belgium	6000
12	Research Site	Gent		Belgium	9000
13	Research Site	Haine-Saint-Paul		Belgium	7100
14	Research Site	Leuven		Belgium	3000
15	Research Site	Libramont-Chevigny		Belgium	6800
16	Research Site	Namur		Belgium	5000
17	Research Site	Greenfield Park	Quebec	Canada	J4V 2H1
18	Research Site	Montreal	Quebec	Canada	H1T 2M4
19	Research Site	Montreal	Quebec	Canada	H3T 1E2
20	Research Site	Paris		France	75005
21	Research Site	Vandoeuvre les Nancy		France	54519
22	Research Site	Batumi		Georgia	6000
23	Research Site	Tbilisi		Georgia	'0112
24	Research Site	Tbilisi		Georgia	'0159
25	Research Site	Tbilisi		Georgia	'0186
26	Research Site	Tbilisi		Georgia	0159
27	Research Site	Tbilisi		Georgia	0186
28	Research Site	Berlin		Germany	10707
29	Research Site	Düsseldorf		Germany	40225
30	Research Site	Essen		Germany	45136
31	Research Site	Köln		Germany	50937
32	Research Site	Budapest		Hungary	1122
33	Research Site	Debrecen		Hungary	4032
34	Research Site	Kaposvár		Hungary	7400
35	Research Site	Kecskemét		Hungary	6000
36	Research Site	Nyíregyháza		Hungary	4400
37	Research Site	Pécs		Hungary	7624
38	Research Site	Szeged		Hungary	6725
39	Research Site	Jerusalem		Israel	91031
40	Research Site	Jerusalem		Israel	9112001
41	Research Site	Nahariya		Israel	22100
42	Research Site	Petah Tikva		Israel	4941492
43	Research Site	Bologna		Italy	40138
44	Research Site	Catanzaro		Italy	88100
45	Research Site	Meldola		Italy	47014
46	Research Site	Messina		Italy	98158
47	Research Site	Milano		Italy	20121
48	Research Site	Milan		Italy	20141
49	Research Site	Monza		Italy	20900
50	Research Site	Napoli		Italy	80131
51	Research Site	Roma		Italy	00128
52	Research Site	Umbria		Italy	5100
53	Research Site	Goyang-si		Korea, Republic of	10408
54	Research Site	Incheon		Korea, Republic of	405-760
55	Research Site	Bydgoszcz		Poland	85-796
56	Research Site	Piła		Poland	64-920
57	Research Site	Rzeszów		Poland	35-021
58	Research Site	Skorzewo		Poland	60-185
59	Research Site	Warszawa		Poland	02-781
60	Research Site	Łódź		Poland	93-513
61	Research Site	Almada		Portugal	2805-267
62	Research Site	Lisboa		Portugal	1400-038
63	Research Site	Lisboa		Portugal	1449-005
64	Research Site	Lisboa		Portugal	1649-035
65	Research Site	Lisboa		Portugal	1998-018
66	Research Site	Loures		Portugal	2674-514
67	Research Site	Porto		Portugal	4099-001
68	Research Site	Kazan		Russian Federation	420029
69	Research Site	Krasnodar		Russian Federation	350040
70	Research Site	Kursk		Russian Federation	305035
71	Research Site	Moscow		Russian Federation	115478
72	Research Site	Moscow		Russian Federation	123056
73	Research Site	Pyatigorsk		Russian Federation	357502
74	Research Site	Ryazan		Russian Federation	390011
75	Research Site	Saint Petersburg		Russian Federation	197082
76	Research Site	Saint-Petersburg		Russian Federation	197758
77	Research Site	Volgograd		Russian Federation	400138
78	Research Site	A Coruña		Spain	15009
79	Research Site	Barcelona		Spain	08035
80	Research Site	Barcelona		Spain	08036
81	Research Site	Barcelona		Spain	08190
82	Research Site	Madrid		Spain	28033
83	Research Site	Madrid		Spain	28050
84	Research Site	Sevilla		Spain	41013
85	Research Site	Zaragoza		Spain	50009
86	Research Site	Cherkasy		Ukraine	18009
87	Research Site	Chernivtsі		Ukraine	58013
88	Research Site	Dnipro		Ukraine	49102
89	Research Site	Kyiv		Ukraine	03039
90	Research Site	M. Kyiv		Ukraine	02094
91	Research Site	S. Khodosivka		Ukraine	08173
92	Research Site	Uzhhorod		Ukraine	88000
93	Research Site	Burton-on-Trent		United Kingdom	DE13 0RB
94	Research Site	Derby		United Kingdom	DE22 3NE
95	Research Site	Leicester		United Kingdom	LE1 5WW