Basket Study for Oligo-metastatic Breast Cancer

Study Overview
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Brief Summary
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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
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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+

Official Title
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Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab deruxtecan


Participation Criteria
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Eligibility Criteria
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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 three, either in one organ or in 2-3 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab-deruxtecan<br>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. | Drug: Trastuzumab deruxtecan<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete radiologic response | Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA | up to one year after start treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients free of progression | as defined by RECIST | assessed up to 10 years | 
| Overall Survival | time from start treatment to death from any cause | assessed up to 10 years | 
| Number of patients with pathological complete response | after resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment | assessed immediately after surgery | 
| Number of patients with metabolic response | as measured with PDG-PET | assessed up to 12 months | 
| Number of patients with metabolic response | as measured by clearance of ctDNA | assessed up to 10 years | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | determined accoriding to CTCAE v5.0 or Clavien-Dindo (in case of surgical resection) | assessed up to 30 days after last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligometastatic disease (max 3 lesions)