Clinical trial NCT05333874: CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage
Official title: CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Breast Cancer, Early-Onset
Keywords: Triple Negative Breast Cancer
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
First posted: 2022-04-19
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: A pilot study to evaluating the role of ctDNA in patients with Stage II-III triple negative breast cancer and HER2 positive breast cancer. Participants who have ctDNA post neoadjuvant therapy and surgery will be initiated on adjuvant systemic therapy per treating physician's choice. ctDNA will be monitored up to 24 months to study ctDNA kinetics. Signatera is intended to detect and quantify how much cancer is left in the body, to improve prognosis and help optimize treatment decisions, based on the tissue-informed testing of mutations.
Primary purpose: DIAGNOSTIC

Brief summary: Primary Objective:

1) To examine the impact of Circulating tumor DNA (ctDNA) (expressed as mean tumor molecules per ml) on treatment decision making in patients with early stage breast cancer after neoadjuvant therapy and surgery

Secondary Objectives:

1. Understand ctNDA kinetics in the neoadjuvant and adjuvant setting
2. To identify any associations between clinical staging and measurable ctDNA

Detailed description: To determine whether early detection of Circulating tumor DNA (ctDNA) after neoadjuvant systemic therapy help tailor adjuvant therapy and reduce risk of relapse in patients who are at increased risk of recurrence. Studies have shown the presence of ctDNA is associated with increased risk of relapse, it is unclear how adjuvant therapy and its effect of ctDNA impacts the risk of relapse. There is very limited data on the role of ctDNA monitoring and response to neoadjuvant/adjuvant systemic therapy in patients with human epidermal growth factor receptor 2 (HER2 ) positive breast cancer.

Natera, Inc. (NASDAQ: NTRA) has developed a minimal residual disease (MRD) assay that sequences tumor tissue to identify a unique signature of tumor mutations, then customizes a personalized PCR assay for each participant, targeting the top 16 clonal mutations found in the tumor (Signatera™). Signatera is intended to detect and quantify how much cancer is left in the body, to improve prognosis and help optimize treatment decisions, based on the tissue-informed testing of mutations.

If the ctDNA blood test is positive, change in treatment can be made after discussion with the participant and treating provider. If the decision is for observation (Observation defined for TNBC: No adjuvant chemotherapy. Participants may complete checkpoint inhibitor from neoadjuvant setting. HER2 positive breast cancer: complete 12 months of anti-HER2 therapy, which was initiated in neoadjuvant setting), participants in the observation arm, will be monitored for ct-DNA re-emergence and systemic therapy can be added at the time of ctDNA re-emergence. If the decision is made to institute systemic therapy based on the ctDNA detection, participants will be monitored with ctDNA at 60days, 3 months, 6 months, 9 months, 12 months, 18months and 24months from surgery. If ctDNA is negative, there will be no change in therapy and participants can continue on observation arm (Observation defined for TNBC: No adjuvant chemotherapy. Participants may complete checkpoint inhibitor from neoadjuvant setting. HER2 positive breast cancer: complete 12 months of anti-HER2 therapy, which was initiated in neoadjuvant setting). Participants in the observation arm will be monitored for ct-DNA re-emergence and systemic therapy can be added at the time of ctDNA re-emergence.

The treating oncologist will complete a questionnaire to determine how ctDNA impacts treatment decisions in the adjuvant setting once the results from the fourteen day ctDNA is available and at the time of ctDNA re-emergence. Participants will complete participant questionnaire at 3 months, 6months,12months and 24 months post-operatively. Participants will be followed up for five years.

Eligibility criteria: Inclusion Criteria:

* Participants with a diagnosis of clinical Stage II-III triple negative and/or HER2 positive breast cancer
* Age ≥ 18 years
* Estimated life expectancy of at least twelve months
* Participant must be eligible for neoadjuvant systemic therapy per treating physician
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Able to provide signed and dated informed consent form
* Must have ctDNA at the time of screening to be eligible for the study
* Participants enrolled on other systemic therapy trials may be eligible to participate in the study after discussion with principal investigator
* Be willing to present for medical exams and blood draws as scheduled per protocol

Exclusion Criteria:

* Evidence of metastatic breast cancer
* Any other concurrent malignancy
* Prior malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least one year prior to study entry
* Participant is pregnant
* Serious concomitant systemic disorder that would compromise the safety of the participant or compromise the participant's ability to complete the study, at the discretion of the investigator
* Bone marrow transplant or other organ transplant recipient
* History of psychiatric illness or social situations that would limit compliance with study requirements
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Primary outcomes:
measure: Detectable Circulating tumor DNA ctDNA
timeFrame: Five Years
Secondary outcomes:
measure: Levels of Detectable Circulating tumor DNA ctDNA
timeFrame: Five Years
Other outcomes:
Locations:
city: Elizabeth
country: United States
facility: Trinitas Hospital and Comprehensive Cancer Center
state: New Jersey
city: Hamilton
country: United States
facility: RWJBarnabas Health - Robert Wood Johnson University Hospital
state: New Jersey
city: Jersey City
country: United States
facility: Jersey City Medical Center
state: New Jersey
city: Lakewood
country: United States
facility: Monmouth Medical Center - Southern Campus
state: New Jersey
city: Livingston
country: United States
facility: Cooperman Barnabas Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson Barnabas Hospital -Somerset
state: New Jersey
city: Somerville
country: United States
facility: Steeplechase Cancer Center
state: New Jersey
city: West Long Branch
country: United States
facility: Monmouth Medical Center Vantage Point Infusion Cente
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Mridula George, MD
role: PRINCIPAL_INVESTIGATOR
References: