Title
Interim FDG-PET/CT for Predicting Response of HER2+ Breast Cancer to Neoadjuvant Therapy: DIRECT trial

Description
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.

Objective
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.

Treatment Drug: Chemotherapy
Procedure: Computed Tomography
Other: Fludeoxyglucose F-18
Procedure: Positron Emission Tomography
Procedure: Surgical Procedure

Key Eligibility 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.

Applicable Disease Sites
Breast

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Carbone Cancer Center Rockford; UW Health Eastpark Medical Center; UW Health University Hospital