search
Back to results

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

Primary Purpose

Triple Negative Breast Cancer, Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring TNBC, Triple Negative Breast Cancer, Post neoadjuvant, Residual disease, Capecitabine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Capecitabine

Arm Description

1000 mg/m2 administered on Days 1 to 14 of 21-day cycles

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.

Full Information

First Posted
February 19, 2021
Last Updated
January 25, 2023
Sponsor
Stanford University
search

1. Study Identification

Unique Protocol Identification Number
NCT04768426
Brief Title
Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 3, 2021 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer, Breast Cancer
Keywords
TNBC, Triple Negative Breast Cancer, Post neoadjuvant, Residual disease, Capecitabine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Capecitabine
Arm Type
Experimental
Arm Description
1000 mg/m2 administered on Days 1 to 14 of 21-day cycles
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
fluoropyrimidine carbamate
Intervention Description
1000 mg/m2 administered on Days 1 to 14 of 21-day treatment cycles, for 8 cycles.
Primary Outcome Measure Information:
Title
Baseline levels of ctDNA detection
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Correlation of ctDNA levels with genomic features of tumor
Description
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.
Time Frame
24 weeks
Title
Overall Survival (OS)
Description
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).
Time Frame
5 years
Title
Relapse-Free Survival
Description
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.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Anatomic stage I - III triple-negative breast cancer at diagnosis Estrogen receptors (ER) and Progesterone receptors (PR) status <10% 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. ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 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. No evidence of metastatic disease. A minimum 4-week wash out from previous chemotherapy treatment is required. Adequate hematologic function: Absolute neutrophil count (ANC) ≥ 1,500 cells/μL (≥ 1,500/mm3); Platelets ≥ 100,000 cells/μL (≥ 100,000/mm3) 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 Adequate renal function: Serum creatinine ≤ 1.5 x ULN; or calculated creatinine clearance > 50 mL/min using the Cockcroft Gault formula. Planned for 6 months or 8 cycles of adjuvant capecitabine. Women of childbearing potential (WOCBP) must have a negative pregnancy test. WOCBP must agree to use effective contraception during the study and for 3 months after the last dose. 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. 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: Metastatic breast cancer Has not had definitive surgical resection Pregnant or breastfeeding Has not completed definitive adjuvant radiation if planned Known human immunodeficiency virus (HIV) positivity or active hepatitis B or C. Investigational agents within 4 weeks of study initiation Inability to swallow oral medications
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cindy Garcia
Phone
650-497-1681
Email
cinmaig@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melinda Telli
Organizational Affiliation
Stanford Universiy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cindy Garcia
Phone
650-497-1681
Email
cmaigarcia@stanford.edu
First Name & Middle Initial & Last Name & Degree
Melinda Telli, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs