FORESEE: Functional Precision Oncology for Metastatic Breast Cancer: a Feasibility Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- HER2-negative Breast Cancer
- Sponsor
- University of Utah
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Number of cases where clinically actionable outcomes were identified by the use of organoids and drug screening (functional precision oncology).
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a pilot study to assess the feasibility of comprehensive genomic characterization and drug screening in metastatic breast cancer. The trial will seek to provide personalized genomic and drug sensitivity information to eligible patients with metastatic breast cancer prior to disease progression on standard treatment. The trial will also explore how these results influence physician selection of next-line therapy.
Detailed Description
The study will enroll patients with Her2 negative (negative on immunohistochemistry or nonamplified by immunofluorescence in situ hybridization) metastatic breast cancer. Cohorts will enroll according to patient hormone receptor status as hormone receptor-positive or triple-negative. In Part 2, the trial will enroll six patients with triple-negative breast cancer and six patients with ER and/or PR receptor-positive breast cancer. Patients diagnosed with metastatic disease upfront or after a variable interval from completion of definitive therapy for local or locally advanced breast cancer will be eligible. Patients with triple-negative metastatic breast cancer will be offered to participate in the trial at the time of diagnosis. Patients with hormone receptor-positive disease will be offered the option to participate in the study when they have exhausted endocrine monotherapy or endocrine therapeutic combinatorial options. Blood will be collected, and a biopsy will be performed prior to starting the first systemic therapy (triple-negative) or first chemotherapy (hormone receptor-positive). If enough tumor is collected, the patient will be deemed eligible for the trial. Malignant tissue collected from this biopsy will be used for genomic sequencing and for the development of organoid models for drug screening. Drugs selected for sensitivity testing will be guided by the results of the genome analysis and NCCN guidelines. Following tissue acquisition, the patient will begin therapy as selected by the treating physician. This first-line of on study therapy, either standard-of-care or investigational in the context of another existing active clinical trial, will be defined as the first "uninformed" line of therapy. The results from the drug screening and mutation testing will be summarized and returned to the treating physicianbefore the assignment of on study, second-line therapy. Before and after returning results, the treating physician will be administered a survey to assess the potential effect that the precision medicine results have on the selection of the following line of therapy. If a patient begins a therapy that was recommended by the precision medicine results, the therapy will be defined as the "informed" line of therapy. Patient response will be tracked for up to two uninformed lines of therapy. The first line of therapy started after the biopsy will count as the first uniformed line. If a patient does not begin an informed line of therapy after two lines of uninformed therapy they will be taken off study. Response and time of progression will be recorded on both informed and uninformed lines of therapy. The trial will open to enrollment in two stages. Stage One will enroll three patients to assess preliminary program feasibility and to optimize the genomics pipeline and time frames. After enrollment of the first three patients, enrollment will be put on hold. Upon return of results to the treating physicians, the genomics pipeline and time frames will be evaluated. If necessary, the process will be amended to maximize pipeline efficiency and decrease the interval of time between tumor tissue acquisition and the return of results. Stage Two will enroll 12 additional patients to further evaluate on a larger scale our functional precision oncology program in metastatic breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subject aged ≥ 18 years.
- •Her2 negative on immunohistochemistry or nonamplified breast cancer
- •Metastatic or recurrent unresectable breast cancer:
- •Patient with triple-negative breast cancer without prior treatment in the metastatic setting.
- •Patient with hormone receptor-positive breast cancer that has exhausted or refused all endocrine monotherapy or endocrine therapeutic combinatorial options AND has not yet been treated with chemotherapy in the metastatic settings, but for whom chemotherapy is indicated.
- •Willing and capable (per treating investigator's assessment) to undergo baseline tumor collection. Tumor collection may include a solid tumor tissue sample or a fluid sample containing tumor cells.
- •Patient can safely undergo tumor collection:
- •The tumor is reasonably accessible to tumor collection;
- •The tumor is amenable to tumor collection, e.g. does not abut neurovascular structures;
- •If the patient receives anticoagulation, anticoagulation can be safely withheld to accommodate for tissue acquisition;
Exclusion Criteria
- •Diagnosis of any other malignancy with a life expectancy of \< 5 years.
- •The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
- •Myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (\> New York Heart Association Classification Class IIB) or a serious cardiac arrhythmia requiring medication.
- •Renal or liver disease that prohibits the patient from receiving at least single-agent full recommended dose chemotherapy.
- •The patient cannot safely undergo tumor collection for reasons including but not limited to:
- •Tumor is inaccessible;
- •The patient requires anticoagulation which cannot be withheld;
- •The patient has bleeding diathesis;
- •Any other reason that would render tumor tissue acquisition a high-risk procedure.
- •Patient cannot or is unwilling to receive chemotherapy
Outcomes
Primary Outcomes
Number of cases where clinically actionable outcomes were identified by the use of organoids and drug screening (functional precision oncology).
Time Frame: 12 weeks
Determine the feasibility of comprehensive genomic characterization and drug screening for metastatic breast cancer in a clinically relevant time frame.
Secondary Outcomes
- The time from patient sample collection to return of drug screening results.(up to 2 years)
- Performance: comparison between the number of clinically actionable outcomes identified by our functional genomic characterization and commercially available assays(up to 2 years)
- The time from patient sample collection to return of genomic characterization results.(up to 2 years)
- Concordance: To assess the frequency with which our functional precision oncology testing identifies the same therapeutic vulnerabilities identified by commercial (gold standard) testing.(up to 2 years)