Clinical trial NCT05982678: Basket Study for Oligo-metastatic Breast Cancer
Official title: Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HER2-positive Breast Cancer
Keywords: Oligometastatic disease (max 3 lesions)
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo
name: AstraZeneca
First posted: 2023-08-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. In the initial baskets patients with be treated with trastuzumab-deruxtecan.

Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.

The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer patients with 'oligo-metastatic' disease who are usually not included in clinical trials for patients with metastatic disease since loco-regional treatments (radiation, surgery) with curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover, neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases that can be treated with curative intent. This basket trial evaluates T-DXd for oligo-metastatic breast cancer with the goal to induce deep responses and subsequently long-lasting disease remissions and potentially cure.

Detailed description: The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. Given the basket-design of this trial other baskets for oligo-metastatic breast cancer can be added, such as but not limited to other breast cancer subtypes or with other promising drugs.

Baskets for de novo oligo-metastatic disease I. ER+/HER2+ II. ER-/HER2+ Baskets for oligo-metastatic disease after prior chemo/anti-HER2 therapy for primary disease III. ER+/HER2+ IV. ER-/HER2+

Eligibility criteria: Inclusion Criteria:

* Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+ and/or amplification by ISH)\[8\]
* Histologic or cytologic proof of breast cancer metastases (at least one lesion)
* Histologic determination of level of ER-expression
* Oligo-metastatic disease as determined by standard of care diagnostics. The number of total individual distant metastases is limited to five, either in one organ or in 2-5 organ systems. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as single lesion. Pleuritis carcinomatosa, miliary spread of metastases (even within one organ), or peritoneal spread of metastases rules out oligo-metastatic disease and is not allowed. Initial staging by PET-CT (whole body) and MRI of breast and brain are mandatory, as is MRI liver or spine and pelvis in case of liver or bone metastases respectively.
* In case of recurrent disease, a disease-free interval of 24 months.
* Measurable disease according to RECIST1.1
* Patients must be at least 18 years of age and be able to give written informed consent and comply with study procedures.
* World Health Organization (WHO) performance status 0 or 1

Exclusion Criteria:

* prior line of therapy for metastatic disease. Exceptions are endocrine therapy or radiation considered to be part of the curative treatment, within 3 months before enrolment
* leptomeningeal disease or central nervous metastases
* clinically relevant obstruction or compression of spinal cord, central nervous, gastro-intestinal or cardiovascular system, that cannot be alleviated before start of treatment.
* other malignancy, unless treated with curative intention and a long-term survival probability of \>95%, including in-situ or pre-malignant lesions.

Primary outcomes:
measure: Complete radiologic response
timeFrame: up to one year after start treatment
Secondary outcomes:
measure: Number of patients free of progression
timeFrame: assessed up to 10 years
measure: Overall Survival
timeFrame: assessed up to 10 years
measure: Number of patients with pathological complete response
timeFrame: assessed immediately after surgery
measure: Number of patients with metabolic response
timeFrame: assessed up to 12 months
measure: Number of patients with metabolic response
timeFrame: assessed up to 10 years
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: assessed up to 30 days after last treatment
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
Study officials:
affiliation: Antoni van Leeuwenhoek
name: Marleen Kok, MD
role: PRINCIPAL_INVESTIGATOR
References: