Postoperative Circulating Tumor Deoxyribonucleic Acid (ctDNA) Surveillance to Guide the Treatment of Early-Stage Triple Negative Breast Cancer Patients with Residual Disease, PREDICT-RD Trial
This phase II trial studies whether circulating tumor deoxyribonucleic acid (ctDNA) surveillance after surgery (postoperative) can be used to guide the treatment of early-stage triple negative breast cancer (TNBC) patients that have cancer cells in the breast at the time of surgery (residual disease). Every cancer cell has unique deoxyribonucleic acid (DNA). DNA from the tumor may be found in a patient's blood and this is called ctDNA. Looking for ctDNA postoperatively may help find out if the cancer has come back. If ctDNA is found, imaging tests can be used to see if the cancer has come back and spread to other parts of the body. If the cancer has not spread, patients can then be recommended to receive further treatment with datopotamab deruxtecan (DatoDXd). DatoDXd is a monoclonal antibody, called datopotamab, linked to a chemotherapy drug, called deruxtecan. Datopotamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers deruxtecan to kill them. Postoperative ctDNA surveillance may be an effective way to guide the treatment of early-stage TNBC patients with residual disease.
Inclusion Criteria
- ALL PARTICIPANTS: Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
- ALL PARTICIPANTS: Participant is willing and able to comply with study procedures based on the judgment of the investigator
- ALL PARTICIPANTS: Age ≥ 18 years at the time of consent
- ALL PARTICIPANTS: Histological confirmation of TNBC defined by estrogen receptor (ER)/progesterone receptor (PR) < 10%, HER2 0-1+ by immunohistochemistry (IHC) or 2+ by IHC and fluorescence in situ hybridization (FISH) negative
- ALL PARTICIPANTS: Stage II/III TNBC treated with neoadjuvant systemic therapy AND have residual disease defined as RCB II/III at time of surgery
- ALL PARTICIPANTS: Baseline staging scans at the discretion of the treating physician and demonstrates no evidence of metastatic disease
- ALL PARTICIPANTS: The participant must have archival diagnostic tissue and/or surgical resection tissue available
- PARTICIPANTS RECEIVING DATO-DXD: In order to participate in the Dato-DXd cohort a participant must meet ALL of the eligibility criteria required for participation in the study in addition to the Dato-DXd cohort criteria outlined below. Eligibility must be maintained up until the point at which the participant receives treatment for the participant to be considered eligible for treatment
- PARTICIPANTS RECEIVING DATO-DXD: Participants must have signed initial consent for the first part of study within two years
- PARTICIPANTS RECEIVING DATO-DXD: Eastern Cooperative Oncology Group (ECOG) ≤ 2
- PARTICIPANTS RECEIVING DATO-DXD: Participants 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 the investigational regimen are eligible for this trial
- PARTICIPANTS RECEIVING DATO-DXD: Hemoglobin (Hgb) ≥ 8 g/dL (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Platelets ≥ 100 × 10^9/L (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Creatinine ≤ 1.5 × upper limit of normal (ULN) (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Bilirubin ≤ 2 × ULN. Participants with Gilbert’s syndrome may be enrolled despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 × ULN (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Aspartate aminotransferase (AST) ≤ 2 × ULN (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Alanine aminotransferase (ALT) ≤ 2 × ULN (obtained within 14 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- PARTICIPANTS RECEIVING DATO-DXD: Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
- PARTICIPANTS RECEIVING DATO-DXD: Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 7 months after treatment discontinuation and the drug elimination procedure has been completed. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label. Starting at the time of the first dose of study intervention, female subjects/participants must not donate, or retrieve for their own use, ova at any time during this study and for at least 7 months after the last dose of Dato-DXd. Preservation of ova should be considered prior to the first dose of study intervention
- PARTICIPANTS RECEIVING DATO-DXD: Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 4 months after the last dose of study therapy. Starting at the first dose of study intervention, male subjects/participants must not freeze or donate sperm at any time during this study and for at least 4 months after the last dose of Dato-DXd. Preservation of sperm should be considered prior to the first dose of study intervention
- PARTICIPANTS RECEIVING DATO-DXD: Positive ctDNA results for MRD
- PARTICIPANTS RECEIVING DATO-DXD: Radiographic scans (CT chest [C]/abdomen [A]/pelvis [P] -/+ bone scan or PET/CT) within 12 weeks before drug initiation should show no signs of disease recurrence
- PARTICIPANTS RECEIVING DATO-DXD: ≥ 4 weeks from last oral or IV chemotherapy, small molecule inhibitor, biologic, or investigational agent
- PARTICIPANTS RECEIVING DATO-DXD: The participant must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ grade 2 or baseline prior to initiating study treatment
- PARTICIPANTS RECEIVING DATO-DXD: ≥ 4 weeks from last surgery
- PARTICIPANTS RECEIVING DATO-DXD: ≥ 2 weeks from last dose of radiation
Exclusion Criteria
- ALL PARTICIPANTS: Participant is pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
- PARTICIPANTS RECEIVING DATO-DXD: Active, uncontrolled infection requiring systemic therapy
- PARTICIPANTS RECEIVING DATO-DXD: Uncontrolled or significant cardiac disease
- PARTICIPANTS RECEIVING DATO-DXD: History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
- PARTICIPANTS RECEIVING DATO-DXD: Clinically severed pulmonary compromise resulting from intercurrent pulmonary disease
- PARTICIPANTS RECEIVING DATO-DXD: Leptomeningeal carcinomatosis
- PARTICIPANTS RECEIVING DATO-DXD: Clinically significant corneal disease
- PARTICIPANTS RECEIVING DATO-DXD: Known history of HIV that is not well controlled
- PARTICIPANTS RECEIVING DATO-DXD: Known active or uncontrolled hepatitis B or C infection
- PARTICIPANTS RECEIVING DATO-DXD: Known active tuberculosis infection
- PARTICIPANTS RECEIVING DATO-DXD: Known history of severe hypersensitivity reactions to other monoclonal antibodies
- PARTICIPANTS RECEIVING DATO-DXD: Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd
- PARTICIPANTS RECEIVING DATO-DXD: Concurrent use of systemic hormonal replacement therapy
- PARTICIPANTS RECEIVING DATO-DXD: Major surgical procedure or significant traumatic injury within 3 weeks of the first dose of Dato-DXd, or an anticipated need for major surgery during the study
- PARTICIPANTS RECEIVING DATO-DXD: Receipt of live, attenuated vaccine within 30 days prior to the first dose of Dato-DXd
- PARTICIPANTS RECEIVING DATO-DXD: Receipt of another investigational treatment in the last 4 weeks prior to first dosing
Additional locations may be listed on ClinicalTrials.gov for NCT07069595.
Locations matching your search criteria
United States
North Carolina
Chapel Hill
PRIMARY OBJECTIVE:
I. To evaluate the prevalence of ctDNA-based molecular residual disease (MRD) status in high-risk, early-stage TNBC participants by defining the proportion of TNBC patients with MRD-only recurrence during post-surgery surveillance.
SECONDARY OBJECTIVES:
I. To evaluate the interval between ctDNA positivity and clinically proven relapse.
II. To describe ctDNA levels (including ctDNA clearance) over time in all TNBC participants on study.
III. To evaluate the preliminary efficacy of adjuvant datopotamab deruxtecan (Dato-DXd) in participants with MRD-only TNBC by measuring the proportion of patients who convert from ctDNA positive to negative during therapy (ctDNA clearance).
IV. To evaluate the safety of administration of Dato-DXd in participants with MRD-only TNBC.
V. To evaluate recurrence free survival (RFS) in participants with ctDNA positive and ctDNA negative disease.
VI. To evaluate RFS in participants who receive Dato-DXd.
VII. To evaluate overall survival (OS) in participants with ctDNA positive and ctDNA negative disease.
VIII. To evaluate OS in participants who receive Dato-DXd.
IX. To describe the duration of ctDNA clearance in participants who achieve ctDNA clearance after or during treatment with Dato-DXd.
EXPLORATORY OBJECTIVES:
I. To describe the quality of life in all participants during ctDNA surveillance.
II. To evaluate fear of recurrence in all participants during ctDNA surveillance.
III. To evaluate anxiety in all participants during ctDNA surveillance.
IV. To describe patterns of disease recurrence (locoregional versus [vs] distant recurrence) and analyze the burden of disease at the time of documented clinical recurrence (number of lesions/sites/organs involved).
V. To describe the proportion of patients who have clinically documented distant recurrence who enroll in therapeutic clinical trials in the first-line setting.
VI. To evaluate circulating biomarkers of response in correlation with ctDNA status.
VII. To evaluate genomic and immune predictors of MRD and recurrence through spatial transcriptomics and ribonucleic acid (RNA)/deoxyribonucleic acid (DNA) sequencing of tumor from residual disease and/or tumor at time of recurrence.
VIII. To evaluate the association of residual cancer burden (RCB) as a continuous variable with ctDNA positivity and with outcomes.
IX. To evaluate mutational and transcriptomic differences between residual and untreated disease using whole genome sequencing and bulk RNA sequencing from pre-treatment and surgical samples.
OUTLINE: Patients undergo blood sample collection and ctDNA testing prior to standard of care (SOC) adjuvant therapy. Patients then undergo ctDNA surveillance.
ctDNA SURVEILLANCE: Patients undergo blood sample collection and ctDNA testing once every 6 weeks during SOC adjuvant therapy in the absence of disease progression. Patients who remain ctDNA negative after two cycles of planned adjuvant therapy then undergo blood sample collection and ctDNA testing once every 12 weeks for up to 3 years post-study registration in the absence of disease progression. Patients who are positive for ctDNA and negative for radiographic evidence of recurrence at any point after two cycles of planned adjuvant therapy or up until two years of follow-up may receive Dato-DXd as described in the Dato-DXd sub-study. Additionally, patients undergo computed tomography (CT) and bone scan or positron emission tomography (PET)/CT throughout the study. Patients may also undergo biopsy on study.
DATO-DXD SUB-STUDY: Patients receive Dato-DXd intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and ctDNA testing on cycle 2 day 1 (C2D1), every 6 weeks during Dato-DXd treatment, at end of treatment, and every 12 weeks for 3 years post-study registration. Additionally, patients undergo CT and bone scan or PET/CT during screening. Patients may also undergo CT and bone scan or PET/CT on study and during follow up and biopsy throughout the study.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
Principal InvestigatorYara Abdou
- Primary IDLCCC2215
- Secondary IDsNCI-2025-05695
- ClinicalTrials.gov IDNCT07069595