A multicenter, multicohort, phase 2 platform trial to personalize second-line treatment intensity and targeting in HR-positive, HER2-negative metastatic breast cancer through an integrated liquid biopsy algorithm.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centro Di Riferimento Oncologico Di Aviano

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-03-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Evaluation of a biomarker driven workflow for guiding clinical decision making in second line HR+/HER2- metastatic breast cancer

Secondary objectives 6

1. To describe Progression-free survival (PFS) in patients enrolled in each study arm
2. To describe Overall survival (OS) in patients enrolled in each study arm
3. Evaluation of the somatic mutational profile detected through plasma NGS in patients who are candidate to receiving second line therapy for HR+/HER2- MBC
4. Evaluation of the prognostic impact on PFS and OS of somatic alterations detected through plasma NGS in patients candidate to receiving second line therapy in HR+/HER2- MBC
5. Evaluation of CTCs count detected through CellSearch platform in patients who are candidate to receiving second line therapy for HR+/HER2- MBC
6. Evaluation of the prognostic impact on PFS and OS of a CTCs count ≥ 5/7.5 mL compared to a CTCs count < 5/7.5 mL detected through CellSearch platform in patients candidate to receiving second line therapy in HR+/HER2- MBC

Conditions and MedDRA coding

Metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Female (both pre- and postmenopausal) patients with histologically confirmed diagnosis of adenocarcinoma of the breast with radiological evidence of metastatic disease
2. Estrogen Receptor (ER) and/or Progesteron Receptor (PgR) positive disease confirmed at immunohistochemistry (IHC), as either ER or PR expression ≥ 1%, at the time of metastatic diagnosis. Molecular assessment performed locally on either primary tumor tissue or a biopsy specimen from a metastatic site.
3. HER2 negative breast cancer by FISH or IHC (IHC 0, 1+, 2+ and/or FISH HER2: CEP17 ratio < 2.0) at the time of metastatic diagnosis.
4. Age at the time of signing the informed consent at least 18 years.
5. Disease progression after at least 6 months of first line endocrine therapy with CDK 4/6 inhibitors.
6. The patient must have evaluable disease according to RECIST 1.1 (either measurable or non-measurable)
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
8. Adequate organ function (kidney, bone marrow and liver)
9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of study drugs.
10. Women of childbearing potential must have a negative highly sensitive serum or urine pregnancy test within 7 days prior to randomisation.
11. Female subjects who are breast feeding should discontinue nursing during protocol treatment
12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
13. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained, and documented according to the local regulatory requirements

Exclusion criteria 11

1. Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix
2. Male
3. Previous or synchronous diagnosis of HER2-positive or triple-negative breast cancer
4. Prior chemotherapy for metastatic disease.
5. Disease progression before 6 months of first line endocrine therapy with CDK 4/6 inhibitors
6. Major surgery < 28 days before randomisation
7. Any unresolved toxic effect of prior therapies or surgical procedures of Grade ≥ 2 according to Common Terminology Criteria of Adverse Events (CTCAE v5.0), with the exception of alopecia, peripheral neuropathy and other toxicities not considered a safety risk for the participant at investigator’s discretion
8. Uncontrolled significant active infections (≥ grade 3 according to CTCAE version 5), including active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency Virus (HIV).
9. Uncontrolled intercurrent illness, including psychiatric conditions, that would, in the judgment of the investigator, limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
10. Known hypersensitivity reaction to one of the compounds or substances used in this protocol
11. Pregnant women are excluded from the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical Benefit Rate (CBR), defined as the proportion of patients achieving a Complete response (CR) or Partial response (PR) or Stable disease (SD) lasting at least 6 months, as assessed according to RECIST 1.1 criteria

Secondary endpoints 6

1. Progression Free Survival (PFS), defined as time from second line treatment start until progression or death for any cause, whichever comes first
2. OS, defined as time from second line treatment start until death from any cause
3. Prevalence of somatic alterations detected through plasma NGS in patients who are candidate to receiving second line therapy in HR+/HER2- MBC
4. Prognostic impact on PFS and OS of somatic alterations detected through plasma NGS in patients candidate to receiving second line therapy in HR+/HER2- MBC
5. Proportion of patients with a CTCs count ≥ 5/7.5 mL compared to those with a CTCs count <5/7.5 mL at baseline of second line therapy for HR+/HER2- MBC
6. Prognostic impact on PFS and OS of a CTCs count ≥ 5/7.5 mL with respect to CTCs count < 5/7.5 mL in patients candidate to receiving second line therapy in HR+/HER2- MBC

Investigational products

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

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centro Di Riferimento Oncologico Di Aviano

Sponsor organisation

Centro Di Riferimento Oncologico Di Aviano

Address

Via Franco Gallini 2

City

Aviano

Postcode

33081

Country

Italy

Scientific contact point

Organisation

Centro Di Riferimento Oncologico Di Aviano

Contact name

Lorenzo Gerratana

Public contact point

Organisation

Centro Di Riferimento Oncologico Di Aviano

Contact name

Lorenzo Gerratana

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

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

Documents 13 files

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

Application history

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