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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Jan 2025 → ongoing

Decision date (initial)

2024-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509811-98-00

ClinicalTrials.gov

NCT06450314

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.

Secondary objectives 5

1. Efficacy : • To assess in the ctDNA negative cohort at baseline: - The investigator-assessed progression-free survival (PFS), - The ctDNA dynamics and positivity rate, - The overall survival (OS). - The molecular response - In patients with radiological progression and anti-HER2 treatment has been reintroduced:The Overall Response Rate (ORR),The Duration of Response (DoR).
2. Efficacy : • To investigate prognostic effect on PFS and OS of ctDNA values at specific landmark times (3 months, 6 months, 9 months 12 months, 15 months and 18 months)
3. Efficacy : •To assess among ctDNA positive cohort at baseline: -The PFS , - A patern of progression and treatment in the subsequent line -The OS
4. Quality of life : • To assess the quality of life (QoL) and other patient reported outcomes (PROs) (anxiety and decision regret) in the ctDNA negative cohort
5. Efficacy_To explore in the ctTDNA negative cohort at baseline the above mentionedabovementioned efficacy endpoints according to the subgroups defined by first-line vs later-line

Conditions and MedDRA coding

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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 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;
2. Men or women ≥ 18 years of age;
3. 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);
4. Must have an adequate archival tumor tissue sample available for centralized WES analysis to design the ctDNA test. Requirements: • Sample age: Less than 10 years old. • Preferred sample types (in order of priority): a. Most recent resected tumor tissue sample b. Affected lymph node with adequate cellularity.
5. Patient with ECOG Performance Status (PS) ≤1;
6. 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;
7. In case of bone disease only, complete metabolic response in 18-FDG pet-scanner is required at screening;
8. Patient with treated (surgery and/or radiation therapy) and controlled primary tumor;
9. 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;
10. Adequate cardiac, renal, haematological and hepatic functions according to guidelines hospital;
11. Women of childbearing potential must have a negative serum or urine pregnancy test done within 28 days before inclusion;
12. 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
13. 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;
14. Patients must be affiliated to a Social Security System (or equivalent).

Exclusion criteria 11

1. Any breast cancer progression over the past 2 years or at study entry;
2. Patient concurrently using other approved or investigational antineoplastic agents than trastuzumab, pertuzumab, Trastuzumab-Deruxtecan, TDM-1 +/- endocrine therapy;
3. 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
4. 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;
5. 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
6. 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;
7. Major surgery within 2 weeks prior to study entry
8. Pregnant women or women who are breast-feeding
9. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;
10. 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);
11. Persons deprived of their liberty or under protective custody or guardianship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 9

1. 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.
2. 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.
3. Efficacy : OS will be defined as the time from the date of registration to the date of death due to any cause.
4. 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.
5. 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
6. 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.
7. Quality of Life : QoL will be assessed using the EORTC QLQ-C30 and QLQ-BR45 questionnaire
8. Quality of life : Anxiety will be assessed by the STAI-state questionnaire
9. Quality of life : Decision regret will be assessed by the decision regret scale

Investigational products

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

Test 7

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 · 42 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 15 files

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

Application history

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