Home
Clinical Trials
NCT05710328

Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

235 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-10

Study Completion Date

2029-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This phase II trial tests how well an imaging procedure called fludeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) works in predicting response to standard of care chemotherapy prior to surgery in patients with HER2-positive stage IIa-IIIc breast cancer. FDG is a radioactive tracer that is given in a vein before PET/CT imaging and helps to identify areas of active cancer. PET and CT are imaging techniques that make detailed, computerized pictures of areas inside the body. The use of FDG-PET/CT may help doctors better decide if a patient needs more or less treatment before surgery in order to get the best response. This study evaluates whether FDG-PET/CT is useful in predicting a patient's response to standard of care chemotherapy.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To estimate the negative predictive value (NPV) of neoadjuvant interim (ni)FDG-PET/CT for pathologic complete response (pCR), using delta maximum standardized uptake value corrected for lean body mass day 15 (deltaSULmaxD15), completed through central review, of the primary breast cancer at a threshold of 40%, in patients treated with neoadjuvant HER2-directed therapy.

SECONDARY OBJECTIVES:

I. To estimate the sensitivity, specificity, and positive predictive value (PPV) of niFDG-PET/CT for pCR, using deltaSULmaxD15 of the primary breast cancer at a threshold of 40%, in patients treated with neoadjuvant HER2-directed therapy.

II. To evaluate the performance of niFDG-PET/CT, using deltaSULmaxD15 of the primary breast cancer at a threshold of 40%, as a predictor of 3-year event-free survival (EFS) from time of study registration.

EXPLORATORY OBJECTIVES:

I. To estimate the NPV of niFDG-PET/CT for pCR, using deltaSULmaxD15 of the primary breast cancer at a grid of alternative thresholds ranging from 30% to 60%, in patients treated with neoadjuvant HER2-directed therapy.

II. To compare deltaSULmaxD15 using automated image analysis of FDG-PET/CT by AutoPERCIST (trademark) to standard PET analysis software.

OUTLINE:

Patients receive FDG intravenously (IV), undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8 HER2-Positive Breast Carcinoma Invasive Breast Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Diagnostic (FDG-PET/CT scan)

Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study.

Group Type EXPERIMENTAL

Chemotherapy

Intervention Type DRUG

Receive standard of care chemotherapy

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Fludeoxyglucose F-18

Intervention Type OTHER

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Surgical Procedure

Intervention Type PROCEDURE

Undergo standard of care surgery

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Chemotherapy

Receive standard of care chemotherapy

Intervention Type DRUG

Computed Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Fludeoxyglucose F-18

Given IV

Intervention Type OTHER

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Surgical Procedure

Undergo standard of care surgery

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Chemo Chemotherapy (NOS) Chemotherapy, Cancer, General CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography 18FDG FDG Fludeoxyglucose (18F) fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Operation Surgery Surgery Type Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients (all genders) must be \>= 18 years of age.
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
* Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines that has been determined by local testing.
* Patient must have known (either positive or negative) hormone receptor (estrogen receptor \[ER\] or progesterone receptor \[PR\]) status by local testing, per ASCO/CAP guidelines. Patients with either hormone receptor-positive or hormone receptor- negative HER2-positive breast cancer are eligible.
* Patient must have American Joint Committee on Cancer (AJCC) 8th Edition stage IIa-IIIc according to anatomic staging table at diagnosis and below criteria.

* Patients without nodal involvement (cN0) are eligible if T size \> 2.0 cm (T2-4)
* Patients with nodal involvement (cN1-3) are eligible if T2-4
* Patients with clinical T4d are not eligible
* Patients with bilateral invasive breast cancers are eligible if both cancers are HER2-positive and at least one meets all protocol eligibility criteria and neither cancer renders the patient ineligible.
* Patients with multiple ipsilateral invasive tumors are eligible as long as all tumors are HER2-positive and at least one tumor focus meets all eligibility criteria. Multiple lesions that appear part of the same index tumor do not require additional biopsy/HER2 testing.
* Patient must plan to start a standard neoadjuvant pertuzumab (or other biosimilars) based regimen.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of this imaging intervention are eligible for this trial.
* Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
* Patient must be participating in the trial at an institution which has agreed to perform the imaging research studies, completed the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Center Group (ECOG-ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET/CT scanner approval.

* For patients who completed the baseline (T0) FDG-PET/CT PRIOR to registration, neoadjuvant pertuzumab-based regimen must start after study registration and within 21 days after the T0 scan.

* Patients must not have used colony stimulating growth factors within 14 days prior to completing a T0 scan done prior to registration.

Exclusion Criteria

* Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy.
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the teratogenic effects of FDG in addition to the radiation exposure during PET/CT. All patients of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy.

* NOTE: A pregnancy test within 7 days prior to the T0 scan is also required but will only need to be done if a) the T0 scan is completed after study registration and b) if the pregnancy test done prior to registration is completed outside of the 7-day window.

A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

* Patient must not have any contraindication to FDG-PET/CT imaging which includes routine glucose values \> 200 mg/dL and severe claustrophobia.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Heather Jacene

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status RECRUITING

Cancer Center at Saint Joseph's

Phoenix, Arizona, United States

Site Status RECRUITING

Los Angeles General Medical Center

Los Angeles, California, United States

Site Status RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Saint John's Cancer Institute

Santa Monica, California, United States

Site Status RECRUITING

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status RECRUITING