Clinical trial NCT06663787: Personalized Detection of CtDNA for Patients with HER2-Positive Metastatic Breast Cancer Who Achieved Durable Response by Anti-HER2 Treatment (HER2 CR)
Official title: Personalized Detection of CtDNA for Patients with HER2-Positive Metastatic Breast Cancer Who Achieved Durable Response by Anti-HER2 Treatment (HER2 CR)
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Breast Cancer, Metastatic
HER2 + Breast Cancer
Keywords: ctDNA monitoring
MRD
minimal residual disease
HER2+ breast cancer
Dual response
Lead sponsor: Nagoya City University
Sponsor class: OTHER
First posted: 2024-10-29
Enrollment: 50
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The eligibility criteria for this study include patients who have been diagnosed with histologically confirmed invasive breast cancer and unresectable HER2-positive breast cancer. Eligible cases are those in which drug therapy, including anti-HER2 therapy, was initiated between January 1, 2000, and December 31, 2021. Additionally, patients must have maintained a partial or complete response to drug therapy, including anti-HER2 therapy, for more than two years. Finally, the study is limited to female patients aged 20 years or older.

Brief summary: Anti-HER2 therapy, such as trastuzumab and pertuzumab, has significantly improved long-term survival in HER2-positive breast cancer. The updated data of the CLEOPATRA trial showed significant Kaplan-Meier curves, suggesting the potential for a cure. However, the efficacy of maintenance therapy in long-term responders remains unexplored. This study will assess MRD in unresectable HER2-positive breast cancer cases with long-term response using the Signatera™ ctDNA assay, which could contribute to future treatment strategy development.

Detailed description: More than 20 years have passed since the introduction of trastuzumab as a treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The additive effect of trastuzumab, an anti-HER2 antibody, was evaluated in combination with chemotherapy (paclitaxel or anthracycline plus cyclophosphamide) in previously untreated, unresectable HER2-positive breast cancer. The number of cases achieving long-term survival with anti-HER2 therapy has been increasing, and this trend is also observed in our institution.

The treatment for unresectable breast cancer is systemic therapy, which is typically continued as long as it remains effective and side effects are tolerable. However, in cases of long-term response in HER2-positive breast cancer, the impact of continuing anti-HER2 therapy alone as maintenance therapy on prognosis and the safety of treatment discontinuation remains unclear.

In recent years, the clinical application of circulating tumor DNA (ctDNA) has attracted attention for early diagnosis and detection of minimal residual disease. Signatera™, an assay developed by Natera Inc., detects minimal residual disease. It is a personalized ctDNA test for individual patients, and a study targeting breast cancer patients post-surgery reported a detection sensitivity exceeding 90% for variant allele frequencies (VAF) as low as 0.01%. This high sensitivity has been reported not only in breast cancer but also in other cancer types. However, there have been no reports of Signatera analysis in unresectable breast cancer.

In this study, investigators will use Signatera™ to evaluate and analyze ctDNA status (ctDNA positive or negative) in cases of unresectable HER2-positive breast cancer that have achieved long-term response. By assessing ctDNA in such cases, this study may lead to new therapeutic strategies, such as de-escalating anti-HER2 therapy in ctDNA-negative cases.

Eligibility criteria: Inclusion Criteria:

* HER2 + metastatic breast cancer
* Pre / post menopausal
* Previously treated with anti-HER2 therapy
* Continuing CR or PR for more than 2 year

Exclusion Criteria:

* Patients who were deemed inappropriate as research subjects based on the physician's judgment, such as those possibly receiving inappropriate treatment.

Primary outcomes:
measure: The status of ctDNA
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: San Carlos
country: United States
facility: Natera
state: Texas
city: Nagoya
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya City University
state: Aichi
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Study officials:
References: