Breast Cancer Metastatic, Breast Cancer Stage IV
Conditions
Keywords
HR+, HER2 low, HER2 ultralow, molecular screening, ctDNA, T-DXd, Antibody-drug conjugate, trastuzumab deruxtecan, Breast cancer metastatic
Brief summary
After an initial screening phase to identify patients with persistent blood circulating DNA tumors, patients will be enrolled in the treatment phase that was designed as an open-label, multicentre, phase II study, to test the efficacy of trastuzumab deruxtecan in terms of progression-free survival (PFS).
Detailed description
Eligible patients to the screening phase are patients with hormone receptor positive (estrogen receptor and/or progesterone receptor \>10%) and HER2 low or ultralow metastatic breast cancer who will receive standard first line therapy with CDK4-6i (any from the market), combined with aromatase inhibitor or fulvestrant. Patient persistence of tumor DNA in the blood at 4 weeks of this standard therapy will be included in the treatment phase with trastuzumab deruxtecan (T-DXd).
Interventions
DRUGtrastuzumab derxutecan
T-DXd will be administrated as an intra-venous injection of 5.4 mg/kg every three weeks (1 cycle = 21-day treatment).
Sponsors
UNICANCER
AstraZeneca
Breast Cancer Research Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
After an initial screening phase to identify patients with blood circulating tumours persistent, patients will be enrolled in the treatment phase that was designed as an open-label, multicentre, phase II study, to test the efficacy of trastuzumab deruxtecan in terms of progression-free survival (PFS).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
SCREENING PHASE\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Inclusion criteria 1. Patient must have signed the written informed consent for screening phase prior to any trial specific procedures. Note: 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 writing the patient's consent. 2. Patient is ≥18 years of age. 3. Documented breast cancer that: * Is metastatic and eligible to biopsy for subsequent histological or cytological confirmation, * Is HER2 low (HER2 1+, or 2+ and in situ hybridization (ISH) negative) or HER2 ultra low (IHC 0 with incomplete and faint membrane staining in \>0 and ≤10% of tumor cells) on the most recent tumor material available, as defined by the local pathologist under ASCO/CAP guidelines, * Is HR-positive (positive for estrogen receptor or progesterone receptor ≥10% of tumor cell nuclei are immunoreactive) in the metastatic setting. 4. Patient has either: * a metastatic relapse during or within 1 year after termination of the adjuvant endocrine therapy (AI resistant), or * a metastatic relapse more than one year of completing adjuvant AI or a de-novo metastatic breast cancer (AI sensitive/naive). 5. For AI resistant population: patient has previously gone through the ctDNA screening part of the SAFIR 03 - SCREENING/ARRIBA study and fulfilled all the inclusion criteria and none of the
Exclusion criteria
. 6. Patient did not receive any therapy in the metastatic setting. 7. Patient is eligible for a first-line treatment with a marketed CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in combination with either AI or fulvestrant, according to its marketing authorisation. 8. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. 9. Patient has an adequate bone marrow and organ function. 10. Patient has a measurable or an evaluable disease according to Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1). 11. Availability of an archived metastatic tumor sample (FFPE) for exploratory research. Bone metastasis are accepted if tissue is representative of tumor tissue (at least 10% tumor cellularity). 12. Patient must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures. 13. Registration in a National Health Care System (or equivalent).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From first treatment administration to disease progression or death, up to 5 years | The progression-free survival is the length of time during and after treatment of the disease with T-DXd that a patient lives with the disease but it does not get worse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From the first T-DXd administration to death due to any cause, up to 5 years | The overall survival is the length of time from first T-DXd administration that patients enrolled in the study are still alive. |
| Objective response Rate (ORR) | From first T-DXd Administration to 6 months after the first administration of treatment, up to 5 years | The objective response rate is defined as the percentage of patients with a complete response (CR) or a partial response (PR) for a T-DXd treatment. |
| Duration of response (DoR) | From the date of first documentation to disease progression or death, up to 5 years | The time from first documented response (CR or PR) until the date of the first disease progression or death from any cause, whichever occurs first. |
| Clinical benefit rate (CBR) | From first T-DXd Administration to 6 months after the first administration of treatment, up to 5 years | The clinical benefit risk is defined as the proportion of patients with at least a confirmed CR, PR, or a stable disease for 6 months or more after the first administration of treatment. |
| Time to response (TTR) | From the first T-DXd administration to objective response, up to 5 years | The time to response is defined as the time from the first T-DXd administration to the first documentation of CR or PR. |
| Toxicity during the study | Throughout study completion, up to 5 years | The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORFabrice ANDRE, MD
Gustave Roussy, Cancer Campus, Grand Paris
Outcome results
None listed