Circulating Tumor DNA to Guide Changes in Standard of Care Chemotherapy
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVanderbilt-Ingram Cancer Center
About this trial
This phase II trial tests how well evaluating circulating tumor deoxyribonucleic acid (ctDNA) works to guide therapy-change decisions in treating patients with triple-negative breast cancer (TNBC) that has spread from where it first started (primary site) to other places in the body (metastatic). This study wants to learn if small pieces of DNA associated with a tumor (called circulating tumor DNA, or ctDNA) can be detected in investigational blood tests during the course of standard chemotherapy treatment for breast cancer, and whether information from such investigational ctDNA blood testing could possibly be used as an early indication of chemotherapy treatment failure. It is hoped that additional information from investigational blood testing for ctDNA could help doctors to switch more quickly from a standard chemotherapy treatment that typically has significant side effects and which may not be working, to a different standard treatment regimen against TNBC, called sacituzumab govitecan. Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a chemotherapy drug, called irinotecan. hRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers irinotecan to kill them. Studying ctDNA may assist doctors to change therapy earlier if needed, and may improve health outcomes in patients with metastatic TNBC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
In-situ hybridization (ISH) non-amplified (ratio of HER2 to CEP17 < 2.0 or
Single probe average HER2 gene copy number < 4 signals/cell), or
Immunohistochemistry (IHC) 0 or IHC 1+ (if more than one test result is available and not all results meet the inclusion criterion definition, all results should be discussed with the sponsor-investigator to establish eligibility of the patient)
ER and PR negativity are defined as =< 10% of cells expressing hormonal receptors via IHC analysis
Disqualifiers
Leptomeningeal disease
Uncontrolled tumor-related pain: patients requiring narcotic pain medication must be on a stable regimen at registration. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization
Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Malignancies other than TNBC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
Trial design
Design model
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection for banking
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection for ctDNA evaluation
Sacituzumab Govitecan
Biological/VaccineGiven by IV
Treatment groups
160 Participants
are divided into 2 treatment groupsGroup A: Arm A (biospecimen banking)Active comparator 3 interventions
Group B: Arm B (biospecimen evaluation, possible treatment change)Experimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Progression-free survival (PFS)
The study survival will be estimated using the Kaplan-Meier method with 95% confidence intervals (CIs). The CI based on the Greenwoods variance will be reported. In addition, the efficacy of the study groups will be compared for PFS with log-rank tests. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age, on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence intervals will be reported.
Time frame
Up to 3 yearsSecondary outcomes
1
Incidence of adverse events
Adverse events will be graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events version 5.0. Adverse medical events will be tabulated. NCI toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
Time frame
From initiation of study-indicated treatment until 30 days after final study-indicated treatment or until initiation of another anticancer therapy, whichever occurs first2
Progression free survival 2
The study survival will be estimated using the Kaplan-Meier method with 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the efficacy of the study groups will be compared for PFS2 with log-rank tests. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age, on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence intervals will be reported.
Time frame
Up to 3 years3
Overall survival (OS)
The study survival will be estimated using the Kaplan-Meier method with 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the efficacy of the study groups will be compared for OS with log-rank tests. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age, on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence intervals will be reported.
Time frame
Up to 3 years4
Response rate (RR)
The exact two-sided 95% confidence intervals for the RR will be reported for each arm. The Fisher's exact test will be used to examine the difference of RR between treatment arms.
Time frame
Up to 3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Vanderbilt-Ingram Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov