Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer

Phase II Trial of Circulating Tumor DNA Monitoring During Adjuvant Capecitabine in Patients With Triple-negative Breast Cancer and Residual Disease Following Standard Neoadjuvant Chemotherapy

The purpose of the study is to evaluate the use of a circulating tumor DNA (ctDNA) assay, ie, a "liquid biopsy," as a tool to identify triple-negative breast cancer (TNBC) patients who will or will not experience benefit from treatment with capecitabine. Participants will be monitored for changes in ctDNA in the blood over time received during capecitabine treatment. Results of ctDNA analysis will be correlated to genetic characteristics of individual tumors. This may inform future clinical trials in which patients could receive a different treatment than capecitabine to reduce their risk of breast cancer relapse.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Capecitabine

Detailed Description

The Primary Objective is to characterize the circulating tumor DNA (ctDNA) profile of triple-negative breast cancer (TNBC) in participants with residual disease after standard neoadjuvant chemotherapy (NAC) receiving standard-of-care adjuvant capecitabine.

The Secondary Objectives are to correlate ctDNA levels with genomic features and survival.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vishal Joshi; Phone Number: 650-725-7489; Email: vishalj4@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94304
      • Recruiting
      • Stanford University
      • Principal Investigator: Melinda Telli, MD
      • Contact: Vishal Joshi; Phone Number: 650-725-7489; Email: vishalj4@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Anatomic stage I - III triple-negative breast cancer at diagnosis
2. Estrogen receptors (ER) and Progesterone receptors (PR) status <10%
3. Residual disease following at least 4 cycles of neoadjuvant chemotherapy. Patients who received other investigational immunotherapy or targeted therapy during the neoadjuvant phase of treatment are eligible.
4. ≥ 18 years of age
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
6. All clinically significant toxic effects of prior cancer therapy resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v 5.0), except alopecia and G2 neuropathy.
7. No evidence of metastatic disease.
8. A minimum 4-week wash out from previous chemotherapy treatment is required.
9. Adequate hematologic function: Absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); Platelets ≥ 100,000 cells/μL (≥ 100,000/mm3)
10. Adequate hepatic function: Bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN). Exception: If Gilbert's syndrome; then ≤ 5 times ULN. Aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN
11. Adequate renal function: Serum creatinine ≤ 1.5 x ULN; or calculated creatinine clearance > 50 mL/min using the Cockcroft Gault formula.
12. Planned for 6 months or 8 cycles of adjuvant capecitabine.
13. Women of childbearing potential (WOCBP) must have a negative pregnancy test.
14. WOCBP must agree to use effective contraception during the study and for 3 months after the last dose.
15. Male participants and their female partners of child bearing potential must be willing to use an appropriate method of contraception during the study and for 3 months after the last dose.
16. Capable of giving signed informed consent, which includes compliance with requirements and restrictions listed in the informed consent form (ICF) and in the protocol

Exclusion Criteria:

1. Metastatic breast cancer
2. Has not had definitive surgical resection
3. Pregnant or breastfeeding
4. Has not completed definitive adjuvant radiation if planned
5. Known human immunodeficiency virus (HIV) positivity or active hepatitis B or C.
6. Investigational agents within 4 weeks of study initiation
7. Inability to swallow oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capecitabine; 1000 mg/m2 administered on Days 1 to 14 of 21-day cycles	Drug: Capecitabine; 1000 mg/m2 administered on Days 1 to 14 of 21-day treatment cycles, for 8 cycles.; Other Names: fluoropyrimidine carbamate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline levels of ctDNA detection	In participants with triple-negative breast cancer (TNBC) who have received standard neoadjuvant chemotherapy (NAC), levels of circulating tumor DNA (ctDNA) will be assessed at baseline and after 6 months of standard adjuvant capecitabine treatment. The outcome will be reported as the number of participants who are: ctDNA+ (ctDNA-positive) at baseline and at 6 months.; ctDNA+ at baseline but ctDNA- (ctDNA-negative) at 6 months.; ctDNA- at baseline and at 6 months.; ctDNA- at baseline but ctDNA+ at 6 months. The outcome is a number without dispersion.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of ctDNA levels with genomic features of tumor	Genomic status of certain mutations in the tumor will be assessed by next-generation sequencing in participants who are: ctDNA+ (ctDNA-positive) at baseline and at 6 months.; ctDNA+ at baseline but ctDNA- (ctDNA-negative) at 6 months.; ctDNA- at baseline and at 6 months.; ctDNA- at baseline but ctDNA+ at 6 months. The genes of interest are: PIK3CA AKT AKT1 PTEN BRCA1 BRCA2 PALB2 CHEK2 ATM NBN BRIP1 BARD1 MRE11 ATR RAD50 RAD51C RAD51D FANCA FANCC FANCD2 FANCE FANCF FANCG FANCL. The outcome will be reported as the number of participants with a positive mutation status in the gene of interest. The outcome is a number without dispersion.	24 weeks
Overall Survival (OS)	Overall survival (OS) will be assessed as participants remaining alive 5 years from the first treatment initiation. The outcome is reported as the number of participants alive (without dispersion).	5 years
Relapse-Free Survival	Relapse-free survival is defined as the time from treatment initiation to first invasive relapse or death, through 5 years. The outcome is reported as the number of participants with relapse-free survival (without dispersion) at 5 years.	5 years

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Melinda Telli, Stanford Universiy

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Capecitabine; TNBC; Triple Negative Breast Cancer; Post neoadjuvant; Residual disease
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm, Residual; Breast Neoplasms; Triple Negative Breast Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine
• Other Study ID Numbers: IRB-57723; NCI-2021-01757 (Other Identifier: National Cancer Institute Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes