Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial
Interim FDG-PET/CT for PreDIcting REsponse of HER2+ Breast Cancer to Neoadjuvant Therapy: DIRECT Trial
3 other identifiers
interventional
235
2 countries
102
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2023
Longer than P75 for phase_2
102 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 24, 2023
CompletedFirst Posted
Study publicly available on registry
February 2, 2023
CompletedStudy Start
First participant enrolled
May 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2029
May 5, 2026
April 1, 2026
4.1 years
January 24, 2023
April 29, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Negative predictive value of neoadjuvant interim (ni) fludeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) for pathologic complete response (pCR)
The analysis set for this objective will comprise all patients who enrolled in the study and had a FDG-PET/CT scan at T0 and T1 timepoint. The negative predictive value is defined as the probability that pCR will not be achieved by study participants who experience a using delta maximum standardized uptake value corrected for lean body mass day 15 (deltaSULmaxD15) below 40% and will be estimated via an exact, two-sided 95% confidence interval.
Up to 5 years
Secondary Outcomes (4)
Sensitivity of niFDG-PET/CT for pCR
Up to 5 years
Specificity of niFDG-PET/CT for pCR
Up to 5 years
Positive predictive value of niFDG-PET/CT for pCR
Up to 5 years
Performance of niFDG-PET/CT as predictor of 3-year event-free survival
Up to 5 years
Other Outcomes (2)
Negative predictive value of niFDG-PET/CT for pCR
Up to 5 years
Compare deltaSULmaxD15 using automated image analysis of FDG-PET/CT by AutoPERCIST (trademark) to standard PET analysis software
Up to 5 years
Study Arms (1)
Diagnostic (FDG-PET/CT scan)
EXPERIMENTALPatients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study.
Interventions
Receive standard of care chemotherapy
Undergo PET/CT
Given IV
Undergo PET/CT
Undergo standard of care surgery
Eligibility Criteria
You may qualify if:
- 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.
- +2 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (102)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, 85004, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Saint John's Cancer Institute
Santa Monica, California, 90404, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813, United States
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813, United States
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Castle Medical Center
Kailua, Hawaii, 96734, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, 96766, United States
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701, United States
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301, United States
Northwestern University
Chicago, Illinois, 60611, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
Louisiana State University Health Science Center
New Orleans, Louisiana, 70112, United States
University Medical Center New Orleans
New Orleans, Louisiana, 70112, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Minnesota Oncology - Burnsville
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125, United States
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655, United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671, United States
CoxHealth South Hospital
Springfield, Missouri, 65807, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Cooper Hospital University Medical Center
Camden, New Jersey, 08103, United States
Morristown Medical Center
Morristown, New Jersey, 07960, United States
Inspira Medical Center Mullica Hill
Mullica Hill, New Jersey, 08062, United States
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503, United States
Inspira Medical Center Vineland
Vineland, New Jersey, 08360, United States
MD Anderson Cancer Center at Cooper-Voorhees
Voorhees Township, New Jersey, 08043, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Indu and Raj Soin Medical Center
Beavercreek, Ohio, 45431, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Kettering Medical Center
Kettering, Ohio, 45429, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, 19010, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Riddle Memorial Hospital
Media, Pennsylvania, 19063, United States
Bryn Mawr Health Center
Newtown Square, Pennsylvania, 19073, United States
Paoli Memorial Hospital
Paoli, Pennsylvania, 19301, United States
Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania, 18840, United States
Community Medical Center
Scranton, Pennsylvania, 18510, United States
Chester County Hospital
West Chester, Pennsylvania, 19380, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Lankenau Medical Center
Wynnewood, Pennsylvania, 19096, United States
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017, United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120, United States
Dell Seton Medical Center at The University of Texas
Austin, Texas, 78701, United States
University of Texas at Austin
Austin, Texas, 78712, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
FHCC South Lake Union
Seattle, Washington, 98109, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Washington Medical Center - Montlake
Seattle, Washington, 98195, United States
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Marshfield Medical Center - Ladysmith
Ladysmith, Wisconsin, 54848, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Aurora Sinai Medical Center
Milwaukee, Wisconsin, 53233, United States
Marshfield Clinic-Minocqua Center
Minocqua, Wisconsin, 54548, United States
Marshfield Medical Center - Neillsville
Neillsville, Wisconsin, 54456, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Aurora West Allis Medical Center
West Allis, Wisconsin, 53227, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
Marshfield Clinic - Wisconsin Rapids Center
Wisconsin Rapids, Wisconsin, 54494, United States
Cancer Center-Metro Medical Center Bayamon
Bayamón, 00959-5060, Puerto Rico
Doctors Cancer Center
Manati, 00674, Puerto Rico
San Juan Community Oncology Group
San Juan, 00917, Puerto Rico
Centro Comprensivo de Cancer de UPR
San Juan, 00927, Puerto Rico
San Juan City Hospital
San Juan, 00936, Puerto Rico
Related Publications (1)
Hennessy MA, Gatsonis C, Jacene H, Connolly RM, Burnette BL, Stringer-Reasor EM, Romanoff J, Taurone A, O'Sullivan CC, Le-Petross HT, Stearns V, Fowler AM, Tang SC, Sepulveda KA, DeMichele AM, Mankoff DA, Wolff AC. EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial). Future Oncol. 2025 Nov;21(26):3377-3384. doi: 10.1080/14796694.2025.2567840. Epub 2025 Oct 5.
PMID: 41047708DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Heather Jacene
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2023
First Posted
February 2, 2023
Study Start
May 10, 2023
Primary Completion (Estimated)
May 31, 2027
Study Completion (Estimated)
December 31, 2029
Last Updated
May 5, 2026
Record last verified: 2026-04