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

Plain English Summary

Testing the Role of FDG-PET/CT to Predict Response to Therapy Prior to Surgery for HER2-positive Breast Cancer, The DIRECT Trial is a Phase 2 clinical trial sponsored by ECOG-ACRIN Cancer Research Group studying Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2-Positive Breast Carcinoma, Invasive Breast Carcinoma. This study tests an advanced imaging technique (FDG-PET/CT) to see if it can accurately predict how well HER2-positive breast cancer will respond to chemotherapy before surgery. It is for patients diagnosed with HER2-positive breast cancer, stages IIa to IIIc, who are scheduled to receive standard chemotherapy before surgery. Participation involves undergoing a special type of scan (FDG-PET/CT) at specific times during the chemotherapy treatment. Standard treatment for this type of breast cancer typically involves chemotherapy, surgery, and sometimes radiation or hormone therapy, but this study focuses on optimizing the chemotherapy phase. The trial aims to enroll 235 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older and have been diagnosed with HER2-positive invasive breast cancer that is stage IIa to IIIc. You must be able to consent to participate and have a general health status that allows for treatment (ECOG 0-2). You cannot have had any prior treatment for your current breast cancer, including surgery, chemotherapy, radiation, or hormone therapy. You cannot be pregnant or breastfeeding, and women of childbearing potential must have a negative pregnancy test. This trial is studying Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2-Positive Breast Carcinoma, Invasive Breast Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how accurately the FDG-PET/CT scan can identify patients whose cancer is likely to be completely eliminated by the chemotherapy before surgery. The specific primary outcome measures are: 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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial matters because it seeks to improve treatment decisions for HER2-positive breast cancer by identifying early on which patients are responding well to chemotherapy, potentially avoiding unne Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2-Positive Breast Carcinoma, Invasive Breast Carcinoma, where improved treatment options are needed.

Investor Insight

This trial addresses a critical need in optimizing neoadjuvant therapy for HER2+ breast cancer, a significant market within oncology, with the potential to refine treatment protocols and improve patie Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this imaging test is appropriate for you and how it might change your treatment plan. You will have at least one special scan (FDG-PET/CT) during your chemotherapy treatment, which involves an injection of a radioactive tracer and then imaging. Your treatment will proceed as planned with standard chemotherapy and surgery, but the scan results may help guide future treatment decisions. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 235 participants

Interventions

• DRUG: Chemotherapy — Receive standard of care chemotherapy
• PROCEDURE: Computed Tomography — Undergo PET/CT
• OTHER: Fludeoxyglucose F-18 — Given IV
• PROCEDURE: Positron Emission Tomography — Undergo PET/CT
• PROCEDURE: Surgical Procedure — Undergo standard of care surgery

Primary Outcomes

• 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)

Secondary Outcomes

• 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)

Full Eligibility 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.

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Cancer Center at Saint Joseph's, Phoenix, Arizona, United States
• Los Angeles General Medical Center, Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
• Saint John's Cancer Institute, Santa Monica, California, United States
• Sibley Memorial Hospital, Washington D.C., District of Columbia, United States
• Mayo Clinic in Florida, Jacksonville, Florida, United States
• 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
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-Positive Breast Cancer
• Invasive Breast Carcinoma
• Anatomic Stage II Breast Cancer
• Anatomic Stage III Breast Cancer
• Neoadjuvant Therapy
• Oncology
• Cancer Imaging
• Chemotherapy
• Personalized Medicine

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