HER2-positive Breast Cancer
Conditions
Keywords
Oligometastatic disease (max 3 lesions)
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+
Interventions
DRUGTrastuzumab deruxtecan
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.
Sponsors
Daiichi Sankyo
AstraZeneca
The Netherlands Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete radiologic response | up to one year after start treatment | Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients free of progression | assessed up to 10 years | as defined by RECIST |
| Overall Survival | assessed up to 10 years | time from start treatment to death from any cause |
| Number of patients with pathological complete response | assessed immediately after surgery | after resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment |
| Number of patients with metabolic response | assessed up to 12 months | as measured with PDG-PET |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | assessed up to 30 days after last treatment | determined accoriding to CTCAE v5.0 or Clavien-Dindo (in case of surgical resection) |
Countries
Netherlands
Contacts
Primary ContactMarleen Kok, MD
Backup ContactRobbert-Jan Gielen, MD
Outcome results
None listed