TriangleNCT06129786 · CITED IN SOURCE DOCUMENTS
Overcoming Therapy Resistance in ER+ Breast Cancer Patients: a Translational Project (OVERTuRE)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- Not reported
- Status at capture
- UNKNOWN
- Registry last update
- 2023-11-13
Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after \>12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor in association with a CDK4/6i. Disease recurrence in \<12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial. A significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics. Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease. * ER positive tumor ≥ 1% * HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio \< 2.0) * Females, 18 years of age or older * Candidate to first-line endocrine therapy (LH-RH analogue for pre-menopausal women is allowed) * Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. * Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures. Exclusion Criteria: * 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. * Prior endocrine therapy for metastatic disease * Prior chemotherapy for metastatic disease * Patients unwilling to or unable to comply with the protocol. * Known CNS metastases
- minimum Age
- 18 Years
- sampling Method
- NON_PROBABILITY_SAMPLE
- sex
- FEMALE
- std Ages
- ADULT
- OLDER_ADULT
- study Population
- Women with hormone receptor-positive ABC, considered eligible for endocrine therapy as first line endocrine treatment
Treatment arms and interventions
Study design
- observational Model
- OTHER
- time Perspective
- PROSPECTIVE
Enrollment
- count
- 74
- type
- ESTIMATED
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Mean difference in mean VAF in most frequently mutated gene found at baseline, with respect to first evaluation after 15 days between responders (CR-PR-SD, Complete Response - Partial Response - Stable Disease) and non-responders (PD, Progressive Disease)
- measure
- To identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like ABC.
- time Frame
- up to 3 years
- description
- Mean difference in mean VAF in most frequently mutated gene found at baseline, with respect to 6 months evaluation between responders (CR-PR-SD, Complete Response - Partial Response - Stable Disease) and non-responders (PD, Progressive Disease)
- measure
- To identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like ABC.
- time Frame
- up to 3 years
- secondary Outcomes
- description
- Differences in time-to-progression (TTP) probability between patients with or without selected ctDNA-based biomarkers. TTP will be defined as the time from first biomarker assessment until objective PD or end of follow-up, whichever comes first.
- measure
- To explore the impact of ctDNA-based biomarkers in terms of treatment resistance
- time Frame
- from first biomarker assessment until objective PD or end of follow-up, up to 3 years
- description
- Differences in progression-free survival (PFS) between patients with or without selected ctDNA-based biomarkers. PFS will be defined as time from beginning of the therapy until objective PD, death or end of follow-up, whichever comes first.
- measure
- To explore the impact of ctDNA-based biomarkers in terms of survival
- time Frame
- from beginning of the therapy until objective PD, death or end of follow-up, up to 3 years
- description
- Differences in Overall survival (OS) between patients with or without selected ctDNA-based biomarkers. OS will be defined as time from beginning of the therapy until death from any cause or end of follow-up, whichever comes first.
- measure
- To explore the impact of ctDNA-based biomarkers in terms of survival
- time Frame
- from beginning of the therapy until death from any cause or end of follow-up, up to 3 years
- description
- Mean difference in mean VAF in most frequently mutated gene found at baseline, between baseline and progression in non-responders (PD, Progressive Disease)
- measure
- Mean difference in mean VAF in most frequently mutated gene found at baseline, between baseline and progression in non-responders (PD, Progressive Disease)
- time Frame
- up to 3 years
Full study description
- brief Summary
- Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after \>12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor in association with a CDK4/6i. Disease recurrence in \<12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial. A significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics. Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.
- detailed Description
- Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after \>12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor (+/- LH-RH analogue depending from the menopausal status) in association with a CDK4/6i. Disease recurrence in \<12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial. The choice of the endocrine backbone and of the CDK4/6i is mostly influenced by the patient's clinical characteristics and by disease factors. However, a significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics. Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.
Source references
Source notices and limitations
Discovery and provenance
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- positive, HER2-negative Advanced or Metastatic Breast Cancer for Initial Endocrine-Based Therapy or After Disease Progression on Endocrine Therapy MONALEESA-3 (NCT06129786) was a randomized (2:1) double-blind, placebo-controlled study of ribociclib in combination with fulvestrant for the treatment of postmenopausal women (N = 726
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Preserved source evidence · Not medical advice