Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial
- Conditions
- Anatomic Stage II Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8Invasive Breast CarcinomaHER2-Positive Breast Carcinoma
- Interventions
- Drug: ChemotherapyProcedure: Computed TomographyOther: Fludeoxyglucose F-18Procedure: Positron Emission TomographyProcedure: Surgical Procedure
- Registration Number
- NCT05710328
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 235
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Patients (all genders) must be >= 18 years of age.
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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.
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Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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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.
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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.
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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
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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.
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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.
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Patient must plan to start a standard neoadjuvant pertuzumab (or other biosimilars) based regimen.
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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.
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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.
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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.
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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.
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Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Diagnostic (FDG-PET/CT scan) Chemotherapy Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study. Diagnostic (FDG-PET/CT scan) Computed Tomography Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study. Diagnostic (FDG-PET/CT scan) Fludeoxyglucose F-18 Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study. Diagnostic (FDG-PET/CT scan) Positron Emission Tomography Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study. Diagnostic (FDG-PET/CT scan) Surgical Procedure Patients receive FDG IV, undergo PET/CT, receive standard of care chemotherapy, and undergo standard of care surgery on study.
- Primary Outcome Measures
Name Time Method Negative predictive value of neoadjuvant interim (ni) fludeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT) for pathologic complete response (pCR) Up to 5 years 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.
- Secondary Outcome Measures
Name Time Method Performance of niFDG-PET/CT as predictor of 3-year event-free survival Up to 5 years Using deltaSULmaxD15 of the primary breast cancer at a threshold of 40%. The analysis set for this objective will be the same as for the primary objective. The analysis will compare estimates of 3-year event-free survival between participants with deltaSULmaxD15 above and below the 40% threshold using a log-rank test.
Specificity of niFDG-PET/CT for pCR Up to 5 years The analysis set for this objective will be the same as for the primary objective. The estimation approach will also be similar.
Sensitivity of niFDG-PET/CT for pCR Up to 5 years The analysis set for this objective will be the same as for the primary objective. The estimation approach will also be similar.
Positive predictive value of niFDG-PET/CT for pCR Up to 5 years The analysis set for this objective will be the same as for the primary objective. The estimation approach will also be similar.
Trial Locations
- Locations (102)
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Centro Comprensivo de Cancer de UPR
🇵🇷San Juan, Puerto Rico
Los Angeles General Medical Center
🇺🇸Los Angeles, California, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Hawaii Cancer Care - Westridge
🇺🇸'Aiea, Hawaii, United States
Saint John's Cancer Institute
🇺🇸Santa Monica, California, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸Lihue, Hawaii, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Bryn Mawr Health Center
🇺🇸Newtown Square, Pennsylvania, United States
Inspira Medical Center Vineland
🇺🇸Vineland, New Jersey, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸Voorhees, New Jersey, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Saint Joseph's Regional Medical Center
🇺🇸Paterson, New Jersey, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Community Medical Center
🇺🇸Scranton, Pennsylvania, United States
Nebraska Medicine-Bellevue
🇺🇸Bellevue, Nebraska, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Baptist Memorial Hospital and Cancer Center-Memphis
🇺🇸Memphis, Tennessee, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Aurora Cancer Care-Southern Lakes VLCC
🇺🇸Burlington, Wisconsin, United States
San Juan Community Oncology Group
🇵🇷San Juan, Puerto Rico
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Guthrie Medical Group PC-Robert Packer Hospital
🇺🇸Sayre, Pennsylvania, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
FHCC South Lake Union
🇺🇸Seattle, Washington, United States
Doctors Cancer Center
🇵🇷Manati, Puerto Rico
Lankenau Medical Center
🇺🇸Wynnewood, Pennsylvania, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Aurora Health Care Germantown Health Center
🇺🇸Germantown, Wisconsin, United States
Marshfield Medical Center - Ladysmith
🇺🇸Ladysmith, Wisconsin, United States
San Juan City Hospital
🇵🇷San Juan, Puerto Rico
Cancer Center at Saint Joseph's
🇺🇸Phoenix, Arizona, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Nebraska Medicine-Village Pointe
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Aurora Saint Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Castle Medical Center
🇺🇸Kailua, Hawaii, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Baptist Memorial Hospital and Cancer Center-Desoto
🇺🇸Southhaven, Mississippi, United States
Aurora Sinai Medical Center
🇺🇸Milwaukee, Wisconsin, United States
Indu and Raj Soin Medical Center
🇺🇸Beavercreek, Ohio, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
Baptist Memorial Hospital and Cancer Center-Collierville
🇺🇸Collierville, Tennessee, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Aurora West Allis Medical Center
🇺🇸West Allis, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Inspira Medical Center Mullica Hill
🇺🇸Mullica Hill, New Jersey, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Baptist Memorial Hospital and Cancer Center-Oxford
🇺🇸Oxford, Mississippi, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Marshfield Medical Center - Neillsville
🇺🇸Neillsville, Wisconsin, United States
Cancer Center-Metro Medical Center Bayamon
🇵🇷Bayamon, Puerto Rico
Hawaii Cancer Care Inc - Waterfront Plaza
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Cenrer - POB I
🇺🇸Honolulu, Hawaii, United States
Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
Queen's Cancer Center - Kuakini
🇺🇸Honolulu, Hawaii, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
The James Graham Brown Cancer Center at University of Louisville
🇺🇸Louisville, Kentucky, United States
Louisiana State University Health Science Center
🇺🇸New Orleans, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Dell Seton Medical Center at The University of Texas
🇺🇸Austin, Texas, United States
Montefiore Medical Center-Einstein Campus
🇺🇸Bronx, New York, United States
University of Texas at Austin
🇺🇸Austin, Texas, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Riddle Memorial Hospital
🇺🇸Media, Pennsylvania, United States
Chester County Hospital
🇺🇸West Chester, Pennsylvania, United States