Decreasing treatment for metastatic HER2-Positive Breast Cancer with undetectable cancer levels in blood tests

Phase 2

Recruiting

Conditions: Patients with HER2-positive locally advanced inoperable or metastatic breast cancer with disease controlled after 2 years of maintenance treatment with anti-HER2 targeted therapy

Registration Number: 2023-509811-98-00

Lead Sponsor: Unicancer

Brief Summary: To evaluate the feasibility of therapeutic de-escalation in HER2-positive metastatic breast cancer with disease controlled after 2 years of maintenance treatment with anti-HER2 targeted therapy AND ctDNA negative testing.

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 170

Inclusion Criteria

Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in signing the patient’s consent;

Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital;

Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion;

Non post-menopausal women and fertile men must agree to use adequate contraception methods during the study. Hormonal contraceptives such as birth control pills, patches, implants, or injections are not allowed in patients who are hormone receptor positive

Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan and other study procedures including follow-up;

Patients must be affiliated to a Social Security System (or equivalent).

Men or women ≥ 18 years of age;

Documented diagnosis of locally advanced inoperable or metastatic histologically-proven HER2-positive breast cancer (HER2-positive is defined as HER2 3+ immunohistochemical overexpression, or the presence of HER2 amplification, according to ASCO-CAP guidelines);

Must have an adequate archival tumor tissue sample available for NGS analysis by central laboratory, in order to design the ctDNA test (based on most recent available tumor tissue sample, metastatic biopsy (bone tissue excluded) and primary tumor authorized);

Patient with ECOG Performance Status (PS) ≤1;

Patient must have received continuous anti-HER2 targeted therapy (including Trastuzumab, Trastuzumab/Pertuzumab, Trastuzumab-Deruxtecan or T-DM1) treatment for at least 2 years in any line setting, for their locally advanced inoperable ormetastatic HER2 + breast cancer (prior treatment interruption of 3 months maximum is allowed), with complete response or partial response at last radiological assessment;

In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required;

Patient with treated (surgery and/or radiation therapy) and controlled primary tumor;

Patients with ER-positive disease may or may not have received concomitant endocrine therapy (which must be continued if present). Concomitant ovarian blockade using LHRH agonists is authorised as well;

Exclusion Criteria

Any breast cancer progression over the past 2 years or at study entry;

Participation in another clinical study whose procedures interfere with those of the study (within 28 days prior to patient enrolment and for the duration of the study);

Persons deprived of their liberty or under protective custody or guardianship.

Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +/- endocrine therapy;

Had an history of tumoral meningitis or clinically active central nervous system metastases, defined as untreated or symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms; a. Subjects with curatively treated brain metastases (i.e., complete removal surgery or stereotactic radiotherapy) who are no longer symptomatic and do not require treatment with corticosteroids or anticonvulsants may be included in the study provided they have recovered from the acute toxicity of radiotherapy and there has been no progression of the brain metastases within the past 24 months. b. Subjects with brain metastases only or treated with whole brain radiotherapy will be excluded of the study

Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient’s participation in this trial or would likely interfere with study procedures or results;

History of any prior ipsi or contralateral breast cancer (except in case of DCIS) unless if both primary tumors were confirmed to be HER2-positive

Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease and treatment for at least 3 years;

Major surgery within 2 weeks prior to study entry

Pregnant women or women who are breast-feeding

Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;

Study & Design

Study Type: Not specified

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The progression-free rate (PFR) defined by radiological, and/or molecular progression. The PFR is defined as the time from the date of registration to the date of the first documented event among radiological progressions (RECIST 1.1), molecular progressions defined by ctDNA+, or death due to any cause, whichever occurs first. Patients alive without any of these events will be censored.		The progression-free rate (PFR) defined by radiological, and/or molecular progression. The PFR is defined as the time from the date of registration to the date of the first documented event among radiological progressions (RECIST 1.1), molecular progressions defined by ctDNA+, or death due to any cause, whichever occurs first. Patients alive without any of these events will be censored.

Secondary Outcome Measures

Name	Time	Method
Quality of life : Decision regret will be assessed by the decision regret scale		Quality of life : Decision regret will be assessed by the decision regret scale
Efficacy : PFS will be defined as the time from the date of registration to the date of the first documented cancer progression measured by RECIST 1.1 or death due to any cause, whichever occurs first. Patients alive without progression will be censored.		Efficacy : PFS will be defined as the time from the date of registration to the date of the first documented cancer progression measured by RECIST 1.1 or death due to any cause, whichever occurs first. Patients alive without progression will be censored.
Efficacy : The ctDNA dynamics is defined as changes in the level of ctDNA (from negative to positive) during the surveillance phase. Positivity rate is defined as the proportion of patients with positive ctDNA.		Efficacy : The ctDNA dynamics is defined as changes in the level of ctDNA (from negative to positive) during the surveillance phase. Positivity rate is defined as the proportion of patients with positive ctDNA.
Efficacy : OS will be defined as the time from the date of registration to the date of death due to any cause.		Efficacy : OS will be defined as the time from the date of registration to the date of death due to any cause.
Efficacy : Molecular response is defined as the percentage of patients who reached molecular remission (ctDNA clearance) 3 months after reintroduction of anti-HER2 treatment among patients with ctDNA positive without RECIST progression.		Efficacy : Molecular response is defined as the percentage of patients who reached molecular remission (ctDNA clearance) 3 months after reintroduction of anti-HER2 treatment among patients with ctDNA positive without RECIST progression.
Efficacy : Objective Response Rate (ORR), defined as the number of patients with at least a confirmed complete response (CR) or partial response (PR) to reintroduction of anti-HER2 treatment, among patients with RECIST progression during the surveillance phase		Efficacy : Objective Response Rate (ORR), defined as the number of patients with at least a confirmed complete response (CR) or partial response (PR) to reintroduction of anti-HER2 treatment, among patients with RECIST progression during the surveillance phase
Efficacy : Duration of Response (Dor) is defined, among patients with RECIST progression during the surveillance phase, as the time from the onset of response after reintroduction of anti-HER2 treatment, to progression or death due to any cause, whichever occurs first.		Efficacy : Duration of Response (Dor) is defined, among patients with RECIST progression during the surveillance phase, as the time from the onset of response after reintroduction of anti-HER2 treatment, to progression or death due to any cause, whichever occurs first.
Quality of Life : QoL will be assessed using the EORTC QLQ-C30 and QLQ-BR45 questionnaire		Quality of Life : QoL will be assessed using the EORTC QLQ-C30 and QLQ-BR45 questionnaire
Quality of life : Anxiety will be assessed by the STAI-state questionnaire		Quality of life : Anxiety will be assessed by the STAI-state questionnaire

Trial Locations

Locations (37): Clinique Pasteur Lanroze
🇫🇷
Brest, France
Oncopole Claudius Regaud
🇫🇷
Toulouse Cedex 9, France
Centre Leon Berard
🇫🇷
Lyon, France
Centre Hospitalier De La Cote Basque
🇫🇷
Bayonne, France
Centre Henri Becquerel
🇫🇷
Rouen, France
Polyclinique Saint-Come
🇫🇷
Compiegne, France
Hopital NOVO
🇫🇷
Pontoise, France
Centre Hospitalier Regional Universitaire De Tours
🇫🇷
Tours, France
Institut Bergonie
🇫🇷
Bordeaux, France
Centre Hospitalier De Bourg-En-Bresse
🇫🇷
Bourg En Bresse, France
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Clinique Pasteur Lanroze
🇫🇷Brest, France
Matthieu CHASSERAY
Site contact
0298313330
m.chasseray@oncologie-brest.fr