Study comparing two standard treatments as initial metastatic treatment among patients with visceral metastasis of ER+ HER2- breast cancer, high burden disease: chemotherapy and combination of hormonotherapy with abemaciclib.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Jun 2020 → ongoing

Decision date (initial)

2024-10-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Lilly France

External identifiers

EU CT number

2024-513005-31-00

EudraCT number

2019-000260-14

ClinicalTrials.gov

NCT04158362

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to compare the efficacy of standard Endocrine Therapy + Abemaciclib combination versus standard Chemotherapy based on progression-free survival (PFS), in patients with visceral metastases of ER+ HER2- breast cancer, high tumor burden.

Secondary objectives 10

1. To compare between the 2 study arms PFS rate at week 24
2. To compare between the 2 study arms Health-Related Quality of Life (HRQOL) and Patient Reported Outcomes (PRO)
3. To compare between the 2 study arms Objective response rate (ORR) and duration of response (DoR)
4. To compare between the 2 study arms Progression-free-survival 1 (PFS 1)
5. To compare between the 2 study arms Progression-free-survival 2 (PFS 2)
6. To compare between the 2 study arms PFS1 and PFS2 in prespecified subgroups defined by stratification factors
7. To compare between the 2 study arms Overall survival (OS)
8. To compare between the 2 study arms Safety
9. In patients randomized in Chemotherapy arm: to describe the maintenance regimens administered after the end of the standard treatment by chemotherapy and in the absence of disease progression.
10. To study the predictive and prognostic value of circulating tumor cell count (< 5 versus >= 5 CTC/7.5 mL) assessed at baseline

Conditions and MedDRA coding

Patients with untreated metastatic Estrogen Receptor positive (ER+), Human Epidermal Growth Factor Receptor-2 negative (HER2-) breast cancer with visceral involvement

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 22

1. Patient must have signed a written informed consent form prior to any study specific procedures
2. Female age ≥ 18 years
3. Performance status, ECOG 0-2
4. Histologically confirmed adenocarcinoma of the breast
5. Metastatic breast cancer, with liver and/or lung and/or pleural and/or peritoneal metastases with high tumor burden (according to RECIST v1.1) defined as either visceral involvement of one site with more than 3 lesions
6. Metastatic breast cancer, with liver and/or lung and/or pleural and/or peritoneal metastases with high tumor burden (according to RECIST v1.1) defined as either visceral involvement of at least 2 sites
7. Metastatic breast cancer, with liver and/or lung and/or pleural and/or peritoneal metastases with high tumor burden (according to RECIST v1.1) defined as either symptomatic ascites or pleural effusion, defined as the need for weekly drainage with visceral measurable metastases
8. Metastatic breast cancer, with liver and/or lung and/or pleural and/or peritoneal metastases with high tumor burden (according to RECIST v1.1) defined as either visceral involvement and LDH > N
9. Patient considered candidate for a first line chemotherapy in metastatic setting by their physician (either capecitabine or paclitaxel) and who may receive first-line endocrine therapy combined with abemaciclib according to the marketed authorization
10. ER-positive by IHC (>10%) on primary or metastatic disease
11. HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative
12. Non-menopausal women will receive LH-RH agonists before starting the endocrine therapy and every 28 days thereafter. It is recommended that LHRH agonist therapy be started approximately 28 days before the start of hormone therapy
13. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 or ≥ 1.5 G/L
14. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Platelets ≥ 100,000/mm3 or ≥ 100 G/L
15. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Hemoglobin ≥ 8 g/dL (patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion)
16. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤ 3 x upper limit of normal (ULN) (< 5 ULN if liver metastasis)
17. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Total serum bilirubin ≤ 1.5 x ULN (patients with Gilbert’s syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted)
18. Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria: Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance > 60 mL/min as calculated using the standard method for the institution
19. Women of childbearing potential agreeing to use highly effective contraception during treatment and for 3 weeks following the last dose of abemaciclib or for 6 months following the last dose of capecitabine or paclitaxel or for 2 years following the last dose of fulvestrant
20. Women of childbearing potential must have a negative serum pregnancy test within 7 days and/or urine pregnancy test 48 hours prior to the administration of any study treatment
21. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
22. Health insurance coverage

Exclusion criteria 19

1. Bone lesion only or non-measurable lesion (RECIST V1.1)
2. Patients with all target lesions in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
3. Spinal cord compression and/or symptomatic or progressive brain metastases (Brain metastasis are not acceptable unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug)
4. Patient with visceral crisis as defined in the 4th ESO–ESMO International Consensus Guidelines (severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease)
5. Patient has received one line of chemotherapy for metastatic disease
6. Patient has received endocrine therapy for metastatic disease
7. Inability to swallow orally administered medication
8. 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
9. Major problem with intestinal absorption
10. Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix or the breast, and adequately treated basal cell or squamous cell carcinoma of the skin
11. Patient has active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment
12. Patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
13. Patient has any serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance < 30 mL/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
14. Any drug or plant derivative that may interact with abemaciclib
15. Episode of pulmonary thromboembolism (PTE) in the last six months. Patients with deep vein thrombosis previously treated with a low-molecular-weight heparin for more than two months prior enrolment in the study will be eligible
16. Patients with previously documented total/partial dihydropyrimidine dehydrogenase (DPD) deficiency or with DPD deficiency identified at baseline visit (plasma uracil concentration ≥ 16 ng/mL). These patients will be not eligible for chemotherapy by capecitabine
17. Pregnant or breast feeding women.
18. Patients enrolled in another therapeutic study within 30 days prior inclusion
19. Individuals deprived of liberty or placed under the authority of a tutor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) will be measured from the date of randomization until the date of event defined as the first documented progression (RECIST v1.1) or death from any cause. Patients with no event at the time of the analysis will be censored at the date of the last available tumor assessment or last follow-up visit whichever comes first. The patients free of progression who switched to another therapy will be censored at the time of the treatment change (RECIST v1.1)

Secondary endpoints 11

1. In both arms throughout treatments A focus will be done at 24 weeks: the progression-free survival (PFS) within 24 weeks will be estimated from the date of randomization until the date of event defined as the first documented progression (RECIST v1.1) or death from any cause
2. In both arms throughout treatments EORTC QLQ-C30 and QLQ-BR23 questionnaires will be used in the measurement of patients’ quality of life. All dimensions will be available at baseline and every 6 weeks during 24 weeks. G8 questionnaire will also be requested at baseline for patient older than 70
3. In both arms throughout treatments Radiological response rates in each treatment arm will be determined according to RECIST v1.1: The overall response rate (ORR) will be defined as the proportion of randomized patients who achieve a complete response (CR) or a partial response (PR) at 24 weeks
4. In both arms throughout treatments Radiological response rates in each treatment arm will be determined according to RECIST v1.1: The duration of response (DoR) will be defined as the duration between the time of tumor response (CR or PR) until the date of objective progression
5. In both arms throughout treatments PFS1: Defined as the interval between the date of randomization and the date of progression or death from any cause regardless of whether the patient withdraws from randomized study treatment or receives another anti-cancer therapy prior to progression
6. In both arms throughout treatments PFS2 : Time from randomization to second progression is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS, or date of death (i.e., objective radiological, CA15-3 or symptomatic progression)
7. In both arms throughout treatments PFS1 and PFS2 in subgroups defined by stratification factors
8. In both arms throughout treatments Overall survival (OS) is defined as the interval between the date of randomization and the date of death from any cause
9. In both arms throughout treatments Safety will be evaluated according to the CTCAE V5.0
10. In patients randomized in Chemotherapy arm: Type of maintenance regimens administered after the end of the standard treatment by chemotherapy and in the absence of disease progression
11. Serial CTC counts will be performed using the CellSearch® system on blood samples to assess predictive and prognostic value of CTC status on overall response rate, PFS within 24 weeks, PFS1 and PFS2 respectively

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications