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Using PET/CT imaging to predict chemotherapy response before surgery for HER2-positive breast cancer

Interim FDG-PET/CT for PreDIcting REsponse of HER2+ Breast Cancer to Neoadjuvant Therapy: DIRECT Trial

Phase 2 Interventional Eastern Cooperative Oncology Group · NCT05710328

This study is testing if a special type of imaging can help predict how well patients with HER2-positive breast cancer will respond to chemotherapy before they have surgery.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment235 (estimated)
Ages18 Years and up
SexAll
SponsorEastern Cooperative Oncology Group Research network
Drugs / interventionspertuzumab, chemotherapy, radiation
Locations102 sites (Birmingham, Alabama and 101 other locations)
Trial IDNCT05710328 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of fludeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) in predicting how well patients with HER2-positive stage IIa-IIIc breast cancer will respond to standard chemotherapy before surgery. Patients will receive FDG intravenously, undergo PET/CT imaging, and then receive standard chemotherapy followed by surgery. The study aims to determine the negative predictive value of FDG-PET/CT for achieving a pathologic complete response, as well as its sensitivity and specificity in this context. Additionally, it will explore the correlation between imaging results and event-free survival over three years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed HER2-positive invasive breast carcinoma who are eligible for neoadjuvant therapy.

Not a fit: Patients with non-HER2-positive breast cancer or those who are not candidates for chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more personalized treatment plans for patients, potentially reducing unnecessary chemotherapy and improving surgical outcomes.

How similar studies have performed: Other studies have shown promising results using imaging techniques to predict treatment responses, suggesting that this approach may be beneficial.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Birmingham, Alabama and 101 other locations

+52 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8HER2-Positive Breast CarcinomaInvasive Breast Carcinoma
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.