ANISE: Basket Study for Oligo-metastatic Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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+
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Trastuzumab-deruxtecan 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
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- Number of patients with metabolic response [assessed up to 10 years]
as measured by clearance of ctDNA
- 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)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+ and/or amplification by ISH)[8]
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Histologic or cytologic proof of breast cancer metastases (at least one lesion)
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Histologic determination of level of ER-expression
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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.
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In case of recurrent disease, a disease-free interval of 24 months.
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Measurable disease according to RECIST1.1
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Patients must be at least 18 years of age and be able to give written informed consent and comply with study procedures.
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World Health Organization (WHO) performance status 0 or 1
Exclusion Criteria:
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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
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leptomeningeal disease or central nervous metastases
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clinically relevant obstruction or compression of spinal cord, central nervous, gastro-intestinal or cardiovascular system, that cannot be alleviated before start of treatment.
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other malignancy, unless treated with curative intention and a long-term survival probability of >95%, including in-situ or pre-malignant lesions.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Antoni van Leeuwenhoek | Amsterdam | Netherlands |
Sponsors and Collaborators
- The Netherlands Cancer Institute
- Daiichi Sankyo, Inc.
- AstraZeneca
Investigators
- Principal Investigator: Marleen Kok, MD, Antoni van Leeuwenhoek
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- M22BOL