UMIN-ICDS Clinical Trial

Public title

Innovation of the 1st line strategy optimized as abemaciclib with endocrine therapy based on the ESR1 mutation of ctDNA for HR-positive HER2-negative advanced metastatic breast cancer patients - Multi-institutional phase 2 trial (JBCRG-M08)

Acronym

JBCRG-M08(AMBER trial)

Scientific Title

Innovation of the 1st line strategy optimized as abemaciclib with endocrine therapy based on the ESR1 mutation of ctDNA for HR-positive HER2-negative advanced metastatic breast cancer patients - Multi-institutional phase 2 trial

Scientific Title:Acronym

JBCRG-M08(AMBER trial)

Region

Japan

Condition

Hormone receptor-positive, HER2-negative inoperable or recurrent breast cancer

Classification by specialty

Hematology and clinical oncology

Breast surgery

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To explore the efficacy of a treatment strategy to select an endocrine agent based on assessment of ESR1 mutation status by ctDNA analysis in patients who continue abemaciclib and aromatase inhibitor combination therapy for at least 6 months as first-line treatment for hormone receptor (HR)-positive, HER2-negative advanced metastatic breast cancer.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

2-year PFS rate from the secondary enrollment (all arms)

Key secondary outcomes

1. 2-year PFS rate after the secondary enrollment (each arm): Key Secondary End Point
2. Rate of disappearance of ESR1 mutations in ctDNA with FUL+ABE: Key Secondary End Point
3. PFS from the secondary enrollment (all arms and each arm)
4. PFS from FUL+ABE initiation (arm FUL+ABE, arm Re-AI+ABE, and both arms)
5. PFS with Re-AI+ABE (arm Re-AI + ABE)
6. Overall survival (OS) (all arms and each arm)
7. Response rate and disease control rate (all arms and each arm)
8. Safety
9. Protocol treatment compliance rate

Study type

Interventional

Basic design

Factorial

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Based on the presence or absence of ESR1 mutation confirmed by "measurement for interventional ctDNA", the content of protocol treatment is continued or changed.

Interventions/Control_2

Based on the presence or absence of ESR1 mutation confirmed by "measurement for interventional ctDNA", the content of protocol treatment is continued or changed.

Interventions/Control_3

Based on the presence or absence of ESR1 mutation confirmed by "measurement for interventional ctDNA", the content of protocol treatment is continued or changed.

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

Inclusion criteria for primary enrollment
1. Histologically diagnosed with invasive breast cancer.
2. Confirmed ER-positive or PgR-positive.
3. Confirmed HER2-negative.
4. Diagnosed with advanced or metastatic breast cancer.
5. Age >=18 years at the time of informed consent.
6. Postmenopausal women.
7. Performance status of 0 or 1
8. Aromatase inhibitor+abemaciclib combination therapy has been administered as the first-line treatment, and both drugs have been continued for >=6 to < 12 months at the time of the primary enrollment.
9. No evidence of progressive disease based on radiographic evaluation within 6 weeks before the day of enrollment.
10. No active interstitial pneumonia confirmed by CT within 6 weeks before the day of enrollment.
11. Non-hematologic toxicities (excluding alopecia) with aromatase inhibitor+abemaciclib combination therapy controlled at Grade <= 2.
12. Meeting the following criteria in blood test within 28 days before the day of enrollment.
13. Patients who received chemotherapy must have recovered (Grade <=1)) . A washout period of at least 21 days is required between last chemotherapy dose and randomization.
14. Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
15. The patient is able to swallow oral medications.
16. Written consent for participation has been obtained from the patient herself.

Inclusion criteria for secondary enrollment
1. Both aromatase inhibitor and abemaciclib have been continued after the primary enrollment and are expected to be continued thereafter.
2. No progression was confirmed by tumor evaluation at Week 12 after the primary enrollment.
3. Performance status (PS) of 0 or 1 according to the ECOG criteria.
4. The patient meets the following criteria in a blood test performed within 28 days before the day of secondary enrollment.

Key exclusion criteria

Exclusion criteria for primary enrollment
1. Patients with ILD/pneumonitits.
2. Patients with central nervous system metastases or carcinomatous meningitis.
3. Patients with active double cancer other than breast cancer.
4. Patients with breast cancer other than hormone receptor-positive, HER2-negative one of synchronous or the disease-free period (< 5 years before the day of primary enrollment).
5. Patients with active systemic bacterial infection.
6. Patients with known infection with HBV or HCV or HIV.
7. Patients with a complication or history of heart failure of NYHA class II to IV, ischemic heart disease, or arrhythmia requiring treatment.
8. Patients with syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin.
9. Patients with poorly controlled diabetes mellitus.
10. Patients with poorly controlled hypertension.
11. Patients with symptoms of dyspnea at rest.
12. Patients with pleural effusion, ascites, or cardiac effusion requiring drainage.
13. Women with childbearing intention, pregnant, or lactating.
14. Patients who do not wish to continue abemaciclib.
15. Patients with major surgery within 14 days prior to randomization.
16. Patients with an experimental treatment in a clinical trial within the last 30 days or 5 half-lives in any other type of medical research.
17. Patients participating or planning to do in other clinical researches.
18. Patients with hypersensitivity to letrozole, anastrozole, fulvestrant, or abemaciclib.
19. Patients with serious and/or uncontrolled preexisting medical condition(s) in the judgement of the investigator.
20. Patients judged by the investigator or subinvestigator to be inappropriate to participate in this research.

Exclusion criteria for secondary enrollment
1. Patients with accompanying active infection requiring systemic treatment.
2. Patients unwilling to continue abemaciclib.
3. Patients judged by the investigator or subinvestigator to be inappropriate to continue this research.

Target sample size

150

Name of lead principal investigator

1st name	Tetsuhiro
Middle name
Last name	Yoshinami

Organization

Osaka University Hospital

Division name

Department of Breast and Endocrine Surgery

Zip code

565-0871

Address

2-15 Yamadaok, Suita-shi, Osaka, Japan

TEL

06-6879-5111

Email

yosinami-te@onsurg.med.osaka-u.ac.jp

Name of contact person

1st name	Jun
Middle name
Last name	Fukase

Organization

Japan Breast Cancer Research Group (JBCRG)

Division name

Head Office

Zip code

103-0016

Address

9-4-3F, Nihonbashi, Koamicho, Chuo-ku, Tokyo, Japan

TEL

03-6264-8873

Homepage URL

https://www.jbcrg.jp/

Email

office@jbcrg.jp

Institute

Japan Breast Cancer Research Group (JBCRG)

Institute

Department

Personal name

Jun Fukase

Organization

Eli Lilly Japan K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Osaka University Clinical Research Review Committee

Address

2-2 Yamadaoka, Suita, Osaka, Japan

Tel

06-6210-8270

Email

handai-nintei@hp-crc.med.osaka-u.ac.jp

Secondary IDs

YES

Study ID_1

jRCTs051220133

Org. issuing International ID_1

jRCT(Japan Registry of Clinical Trials)

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2023

Year

05

Month

18

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2022

Year

06

Month

27

Day

Date of IRB

2022

Year

11

Month

11

Day

Anticipated trial start date

2022

Year

12

Month

14

Day

Last follow-up date

2028

Year

11

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2023

Year

05

Month

18

Day

Last modified on

2023

Year

05

Month

18

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000058218