Breast Cancer, Early-OnsetEarly Phase 1NCT05333874
CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage
A Early Phase 1 study testing Neoadjuvant chemotherapy administered before surgical extraction of a tumor and Observational in people with Breast Cancer, Early-Onset, run by Rutgers, The State University of New Jersey at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Early-Onset
- What is being tested?
- Neoadjuvant chemotherapy administered before surgical extraction of a tumor and Observational
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 12 sitesUnited States
- Study dates
- 6 Apr 2022to 28 Nov 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Trinitas Hospital and Comprehensive Cancer Center
Elizabeth, New Jersey, 07202
RWJBarnabas Health - Robert Wood Johnson University Hospital
Hamilton, New Jersey, 08690
Jersey City Medical Center
Jersey City, New Jersey, 07302
Monmouth Medical Center - Southern Campus
Lakewood, New Jersey, 08701
Cooperman Barnabas Medical Center
Livingston, New Jersey, 07052
Monmouth Medical Center
Long Branch, New Jersey, 07740
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08901
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Robert Wood Johnson Barnabas Hospital -Somerset
Somerville, New Jersey, 08876
Steeplechase Cancer Center
Somerville, New Jersey, 08876
Monmouth Medical Center Vantage Point Infusion Cente
West Long Branch, New Jersey, 07746
About this study
Official title: CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage Breast Cancer
Primary Objective:
- 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:
- Understand ctNDA kinetics in the neoadjuvant and adjuvant setting
- To identify any associations between clinical staging and measurable ctDNA
Read the 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.
- Conditions
- Breast Cancer, Early-Onset
- Being tested
- Neoadjuvant chemotherapy administered before surgical extraction of a tumor, Observational
- Keywords
- Triple Negative Breast Cancer
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant chemotherapy administered before surgical extraction of a tumorDrug
Also called Neoadjuvant chemotherapy
SignateraTM is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The Signatera methodology is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual's tumor tissue. This maximizes accuracy for detecting the presence or absence of disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. 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.
ObservationalOther
Also called No adjuvant chemotherapy
In participants, undetectable ctDNA at fourteen days will be in the observation arm (observation defined as TNBC: No adjuvant chemotherapy. Participants may complete checkpoint inhibitor from neoadjuvant setting; HER2 positive BC: Completed one year of anti-HER2 therapy from the neoadjuvant setting). No investigational drugs will be used. Samples of ctDNA will be collected at time points described in the study arm.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant chemotherapy | Active comparator | If Circulating tumor DNA (ctDNA) blood test is positive, change in treatment can be made. Participants will be monitored with ctDNA at 60days, 3 months, 6 months, 9 months, 12 months, 18months and 24months from surgery.
The participant's core biopsy specimens will be sent to NateraTM to sequence the primary tumor. The baseline blood work for ctDNA will be collected prior to the initiation of systemic therapy. Subsequently, ctDNA will be collected prior to each cycle of neoadjuvant chemotherapy. Participants will undergo surgery and ctDNA needs to be collected fourteen days post-surgery 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. Receives: Drug: Neoadjuvant chemotherapy administered before surgical extraction of a tumor |
| Observational | Other | Observation for triple negative breast cancer (TNBC): No adjuvant chemotherapy. Patients may complete checkpoint inhibitor from neoadjuvant setting. human epidermal growth factor receptor 2 (HER2) positive breast cancer: complete twelve months of anti-HER2 therapy, which was initiated in neoadjuvant setting), participants in the observation arm, will be monitored for Circulating tumor DNA (ct-DNA) re-emergence and systemic therapy can be added at the time of ctDNA re-emergence. Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detectable Circulating tumor DNA ctDNA
Participants with detectable ctDNA fourteen days post-operatively will have the option to change adjuvant therapy after discussion with primary provider. SignateraTM 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.
Measured: Five Years
Secondary outcomes (1)
Levels of Detectable Circulating tumor DNA ctDNA
Participants on observation or change in adjuvant therapy will continue to be monitored with ctDNA at 60 days, 3 months, 6 months, 9 months, 12 months, 18months and 24months from surgery.
Measured: Five Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2022
- Study start6 Apr 2022
- Primary completion28 Nov 2027 (estimated)
- Study completion28 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer, Early-OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rutgers, The State University of New Jersey
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mridula George, MD, Rutgers, The State University of New Jersey
- Investigators
- Mridula George, MD, Principal investigator, Rutgers Cancer Institute of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05333874
- Sponsor's protocol ID
- 042110
- Other IDs
- Pro2022000044
- Status last verified
- Feb 2026
- First submitted
- 12 Apr 2022
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The plan to share IPD will be determined by the PI and updated accordingly.
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CIPHER Study: Pilot Study to Study the Role of ctDNA in Triple Negative and HER2 Positive Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT05333874
- Acronym / sponsor ID
- 042110
- Conditions
- Breast Cancer, Early-Onset
- Keywords
- Triple Negative Breast Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Rutgers, The State University of New JerseyUniversity, hospital or other
- Study start
- 6 Apr 2022 (actual)
- Primary completion
- 28 Nov 2027 (estimated)
- Study completion
- 28 Nov 2027 (estimated)
- First posted
- 19 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- 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:
- Understand ctNDA kinetics in the neoadjuvant and adjuvant setting
- 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant chemotherapy | Active comparator | Drug: Neoadjuvant chemotherapy administered before surgical extraction of a tumorIf Circulating tumor DNA (ctDNA) blood test is positive, change in treatment can be made. Participants will be monitored with ctDNA at 60days, 3 months, 6 months, 9 months, 12 months, 18months and 24months from surgery. The participant's core biopsy specimens will be sent to NateraTM to sequence the primary tumor. The baseline blood work for ctDNA will be collected prior to the initiation of systemic therapy. Subsequently, ctDNA will be collected prior to each cycle of neoadjuvant chemotherapy. Participants will undergo surgery and ctDNA needs to be collected fourteen days post-surgery 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. |
| Observational | Other | Other: ObservationalObservation for triple negative breast cancer (TNBC): No adjuvant chemotherapy. Patients may complete checkpoint inhibitor from neoadjuvant setting. human epidermal growth factor receptor 2 (HER2) positive breast cancer: complete twelve months of anti-HER2 therapy, which was initiated in neoadjuvant setting), participants in the observation arm, will be monitored for Circulating tumor DNA (ct-DNA) re-emergence and systemic therapy can be added at the time of ctDNA re-emergence. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neoadjuvant chemotherapy administered before surgical extraction of a tumorAlso: Neoadjuvant chemotherapySignateraTM is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The Signatera methodology is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual's tumor tissue. This maximizes accuracy for detecting the presence or absence of disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. 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. | Drug | Neoadjuvant chemotherapy |
| ObservationalAlso: No adjuvant chemotherapyIn participants, undetectable ctDNA at fourteen days will be in the observation arm (observation defined as TNBC: No adjuvant chemotherapy. Participants may complete checkpoint inhibitor from neoadjuvant setting; HER2 positive BC: Completed one year of anti-HER2 therapy from the neoadjuvant setting). No investigational drugs will be used. Samples of ctDNA will be collected at time points described in the study arm. | Other | Observational |
Primary outcome
Detectable Circulating tumor DNA ctDNA
Time frame: Five Years
Participants with detectable ctDNA fourteen days post-operatively will have the option to change adjuvant therapy after discussion with primary provider. SignateraTM 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.
1 secondary outcome
Levels of Detectable Circulating tumor DNA ctDNA
Time frame: Five Years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Individual participant dataSharing planned: No. The plan to share IPD will be determined by the PI and updated accordingly.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mridula George, MD principal investigator
Rutgers Cancer Institute of New Jersey
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Neoadjuvant chemotherapy administered before surgical extraction of a tumor and Observational in people with Breast Cancer, Early-Onset, run by Rutgers, The State University of New Jersey at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detectable Circulating tumor DNA ctDNA (time frame: Five Years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026; AzTrials last refreshed its copy on 29 Oct 2026.