ctDNA Monitoring and Neoadjuvant Chemotherapy for Breast Cancer

Not currently recruiting at 11 trial locations

Overseen By Mridula George, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Rutgers, The State University of New Jersey

Disqualifiers: Metastatic cancer, Concurrent malignancy, Pregnancy, Transplant recipient, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 61

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how monitoring circulating tumor DNA (ctDNA)—tiny pieces of tumor DNA in the blood—can guide treatment decisions for patients with early-stage breast cancer. Participants will receive neoadjuvant chemotherapy, administered before surgery, and their ctDNA levels will be checked regularly to determine if treatment adjustments are necessary. The trial also observes changes in ctDNA levels over time and their relation to the cancer's stage. This trial suits those diagnosed with Stage II-III triple-negative or HER2-positive breast cancer who are eligible for chemotherapy before surgery. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It might depend on your specific situation, so it's best to discuss this with the trial's principal investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that neoadjuvant chemotherapy, administered before surgery to shrink tumors, is often used for early-stage breast cancer. Studies have found that patients generally tolerate this type of chemotherapy well. While side effects may occur, they are usually manageable. Common side effects include tiredness, nausea, and hair loss.

Monitoring ctDNA (circulating tumor DNA, tiny pieces of DNA released by cancer cells into the blood) is a non-invasive and safe process. This monitoring can help predict the potential return of breast cancer, providing important information without additional risks.

Overall, while chemotherapy can be challenging, monitoring ctDNA does not introduce extra safety concerns. As this is an early phase trial, safety remains a primary focus, and researchers closely monitor any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how circulating tumor DNA (ctDNA) monitoring can personalize breast cancer treatment. Unlike traditional methods that rely solely on imaging and physical exams, ctDNA offers a real-time glimpse into how a patient's cancer is responding at a molecular level. This approach could help doctors make more informed decisions, adjusting treatments based on ctDNA results to potentially improve outcomes. Additionally, the trial examines how ctDNA can guide treatment for both triple-negative and HER2-positive breast cancer, offering a tailored approach that isn't standard practice yet. This could lead to more precise and effective cancer care in the future.

What evidence suggests that neoadjuvant chemotherapy could be effective for breast cancer?

Research has shown that using chemotherapy before surgery, known as neoadjuvant chemotherapy, holds promise for treating breast cancer, especially when tracked with a blood test called circulating tumor DNA (ctDNA). In this trial, researchers will monitor participants in the neoadjuvant chemotherapy arm with ctDNA at various intervals to assess treatment response. One study found ctDNA in 90% of patients before treatment, and 70.4% of these patients experienced a significant drop in ctDNA levels during treatment, often indicating a positive response to therapy. Another study found that if ctDNA remains after treatment, the risk of cancer returning is higher. These findings suggest that monitoring ctDNA alongside chemotherapy can effectively adjust and improve treatment plans for breast cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Mridula George, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early stage II-III triple negative or HER2 positive breast cancer, who are fit enough for neoadjuvant therapy and surgery. They must have detectable ctDNA, be able to attend medical exams and blood draws, and not be pregnant or have other serious health issues that could affect their participation.

Inclusion Criteria

I am willing to attend all scheduled medical exams and blood tests.

Participants enrolled on other systemic therapy trials may be eligible to participate in the study after discussion with principal investigator

You need to have a blood test for ctDNA when you are screened for the study.

Exclusion Criteria

I have had cancer before, but it was either a non-dangerous skin cancer, a localized cancer that did not spread, or any other cancer that has been in complete remission for over a year.

I do not have any other type of cancer.

I have received a bone marrow or organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy and ctDNA is collected prior to each cycle

Varies based on chemotherapy regimen

Multiple visits for chemotherapy cycles

Surgery and Initial ctDNA Monitoring

Participants undergo surgery and ctDNA is collected fourteen days post-surgery

2 weeks

1 visit for surgery, 1 visit for ctDNA collection

Adjuvant Therapy and ctDNA Monitoring

Participants receive adjuvant therapy based on ctDNA results and are monitored for ctDNA re-emergence

Up to 24 months

Regular visits at 60 days, 3, 6, 9, 12, 18, and 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Neoadjuvant chemotherapy

Trial Overview The CIPHER study is testing the role of circulating tumor DNA (ctDNA) in treatment decisions after pre-surgery chemotherapy and surgical tumor removal in early-stage breast cancer patients. It will also explore how ctDNA levels change during treatment.

How Is the Trial Designed?

Group I: Observational Experimental Treatment 1 Intervention

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.

Group II: Neoadjuvant chemotherapy Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Published Research Related to This Trial

The study involved 31 breast cancer patients and utilized circulating tumor DNA (ctDNA) analysis at three key time points to assess tumor progression and treatment effectiveness, revealing a total of 500 somatic mutations across samples.

Mutations in specific genes like KMT2C in ctDNA were identified as potential indicators of breast cancer recurrence, suggesting that ctDNA could be a valuable tool for monitoring patients over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Circulating Tumor DNA to Predict Neoadjuvant Therapy Effectiveness and Breast Cancer Recurrence. Hao, S., Tian, W., Zhao, J., et al.[2023]

Citations

1. nature.com nature.com/articles/s41698-025-00876-y

Circulating tumor DNA to monitor treatment response in ... In this review, we provide a comprehensive, up-to-date summary of ctDNA in monitoring treatment response with a focus on lung, colorectal, and breast cancers.

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12689-6

Monitoring response to neoadjuvant chemotherapy in triple ... Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e12600

Construction of a model for evaluating the efficacy ... Construction of a model for evaluating the efficacy of neoadjuvant chemotherapy for breast cancer and dynamic monitoring of ctDNA response to ...

4. esmoopen.com esmoopen.com/article/S2059-7029(24)00158-3/fulltext

Circulating tumor DNA for predicting recurrence in patients ... ctDNA detection after neoadjuvant therapy was associated with an increased risk of relapse in both univariate (HR 7.69, 95% CI 4.83-12.24) and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11752932/

Multiple time points for detecting circulating tumor DNA to ... Multiple time points for detecting circulating tumor DNA to monitor the response to neoadjuvant therapy in breast cancer: a meta-analysis. Shuyi ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12420329/

Liquid clues: tracking early-stage breast cancer with ctDNA Several retrospective analyses of clinical trials and cohorts have shown that the monitoring of ctDNA can predict relapses in breast cancer, ...

7. nature.com nature.com/articles/s41523-024-00653-3

Use of ctDNA in early breast cancer: analytical validity and ... This article reviews the data regarding the clinical potential of ctDNA analysis in early BC and the analytical validity of the currently available methods.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1535610823001344

Clinical significance and biology of circulating tumor DNA ... Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive tumor burden assessment.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.502

Detection of circulating tumor DNA following neoadjuvant ... Conclusions: Detection of ctDNA following neoadjuvant chemotherapy, and surgery, is associated with a very high risk of early relapse suggesting ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT06087120

Predicting BReast cAncer Response to neoadjuVant ... This is a prospective and observational study, aiming to determine the detection rate and change of CtDNA in blood samples of cancer patients before, ...