Functional Precision Oncology for Metastatic Breast Cancer
Functional Precision Oncology for Metastatic Breast Cancer
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.
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.
Inclusion Criteria:

 -  Male or female subject aged ≥ 18 years.

 -  Her2 negative on immunohistochemistry or nonamplified breast cancer

 -  Metastatic or recurrent unresectable breast cancer:

 -  Triple-negative breast cancer without prior treatment in the metastatic setting.

 -  OR

 -  Hormone receptor-positive breast cancer that has exhausted or refused all
 endocrine monotherapy or endocrine therapeutic combinatorial options.

 -  Willing and capable (per treating investigator's assessment) to undergo a baseline
 biopsy.

 -  Patient can safely undergo tumor biopsy:

 -  The tumor is reasonably accessible to biopsy;

 -  The tumor is amenable to biopsy, e.g. does not abut neurovascular structures;

 -  If the patient receives anticoagulation, anticoagulation can be safely withheld
 to accommodate for tissue acquisition;

 -  The patient does not have a medical condition that would render a tumor tissue
 acquisition a high-risk procedure, e.g. tumor tissue acquisition from lung
 metastases in a patient with emphysema.

 -  Successful acquisition of a tissue sample containing ≥ 20% tumor content.

 -  Life expectancy of ≥ 6 months as assessed by the treating investigator.

 -  ECOG Performance Status ≤ 2.

 -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
 female pre-menopausal patients. Women will be considered post-menopausal if they have
 been amenorrheic for 12 months without an alternative medical cause. The following
 age-specific requirements apply:

 -  Women < 50 years of age would be considered post-menopausal if they have been
 amenorrheic for 12 months or more following cessation of exogenous hormonal
 treatments and if they have luteinizing hormone and follicle-stimulating hormone
 levels in the post-menopausal range for the institution or underwent surgical
 sterilization (bilateral oophorectomy or hysterectomy).

 -  Women ≥ 50 years of age would be considered post-menopausal if they have been
 amenorrheic for 12 months or more following cessation of all exogenous hormonal
 treatments, had radiation-induced menopause with last menses >1 year ago, had
 chemotherapy-induced menopause with last menses >1 year ago, or underwent
 surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
 hysterectomy).

 -  Able to provide informed consent and willing to sign an approved consent form that
 conforms to federal and institutional guidelines.

 -  At least one lesion (measurable or non-measurable) that can be accurately assessed at
 baseline and is suitable for repeated assessment by computed tomography (CT), magnetic
 resonance imaging (MRI), plain X-ray, or physical examination.

 Exclusion Criteria:

 -  Diagnosis of any other malignancy within 2 years prior to study enrollment, except for
 adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the
 breast, bladder or of the cervix on surveillance with no plans for treatment
 intervention (eg, surgery, radiation, or castration) or radiotherapy and currently
 with no evidence of disease or symptoms is allowed.

 -  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 biopsy 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

 -  Patients with either history of or active spinal cord compression and/or brain
 metastases.