Breast Cancer, Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer
Conditions
Brief summary
There are several approved and guideline-recommended treatments for metastatic, estrogen receptor-positive breast cancer that has progressed on an aromatase inhibitor and a CDK4/6 inhibitor. Right now, doctors do not have a good way of choosing between these treatments. Scientists we work with have come up with ways to use the biology of the tumor to try to predict which treatment is best. This study is being done to test if those predictions are right and to learn more about these tumors to design better treatments in the future.
Detailed description
This is an open-label phase II study of systems biology guided therapy for breast cancer patients positive for Oestrogen receptor after Aromatase inhibitor and CDK inhibition. Based on the SOLAR-1 trial, 25% of tumors would have PIK3CA mutation, so 25% of people would be treated with fulvestrant plus alpelisib with a median PFS in that group of 11 months and 75% of people would be treated with fulvestrant with a median PFS in that group of 6 months.(3) The weighted average of these medians is 7.25 months, but since the actual distributions of the progression free survivals are not available, we will use a conservative estimate of the expected median PFS of the historical control group (fulvestrant +/- alpelisib as second line unguided therapy) of 8 months.
Interventions
All enrolled participants will undergo a tumor biopsy, which will be analyzed for genomic and transcriptomic alterations using FoundationOne (DNA) and Fulgent (RNA). Based on the genomic findings, participants will receive one of the following therapy standard-of-care treatment options: PI3K inhibitor + anti-estrogen therapy ( alpelisib + fulvestrant) MTOR inhibitor + anti-estrogen therapy (everolimus + exemestane) Anti-estrogen therapy alone (fulvestrant monotherapy) Cytotoxic chemotherapy (capecitabine)
Sponsors
City of Hope Medical Center
Inova Health Care Services
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label, interventional
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic diagnosis of breast cancer * Metastatic or incurable * Prior treatment with an anastrozole or letrozole and a CDK4/6 inhibitor * Progression while on or within 6 months of stopping the CDK4/6 inhibitor * At least one lesion amenable to percutaneous biopsy that is not a purely sclerotic bone lesion * ECOG 0-2 * Age 18 or greater * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion criteria
* Prior treatment within 2 years with fulvestrant, alpelisib, everolimus, or capecitabine * Comorbid disease other than breast cancer with a life expectancy of less than 2 years * Cancer other than breast cancer that is expected to need treatment within 2 years * Platelets \< 100,000/microliter * INR \> 1.5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Baseline to 36 Months | No data displayed because Outcome Measure has zero total participants analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Turn Around Time for Systems Biology Analysis | Baseline to 36 Months | No data displayed because Outcome Measure has zero total participants analyzed. |
| Response Rate to Systems Biology Guided Therapy | Baseline to 36 Months | No data displayed because Outcome Measure has zero total participants analyzed. |
| Progression Free Survival Base on Concordance With Recommended Treatment | Baseline to 36 Months | No data displayed because Outcome Measure has zero total participants analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aromatase Inhibitor and CDK Inhibition Drug determined by treating oncologist based on recommendation from systems biology analysis.: All patients will have a biopsy at the beginning of the trial. The biopsy will be sent for DNA sequencing through FoundationOne(clinical test) and RNA profiling at Fulgent(research test) for determination of activation of various oncogenic pathways and phenotypes. The results will be analyzed and a treatment recommendation will be made to the treating physician based on an algorithm. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Aromatase Inhibitor and CDK Inhibition |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Progression Free Survival
No data displayed because Outcome Measure has zero total participants analyzed.
Time frame: Baseline to 36 Months
Population: Two patients enrolled on the study and then withdrew early prior to treatment, therefore no data were collected before study termination.
Secondary
Progression Free Survival Base on Concordance With Recommended Treatment
No data displayed because Outcome Measure has zero total participants analyzed.
Time frame: Baseline to 36 Months
Population: Two patients enrolled on the study and then withdrew early prior to treatment, therefore no data were collected before study termination.
Secondary
Response Rate to Systems Biology Guided Therapy
No data displayed because Outcome Measure has zero total participants analyzed.
Time frame: Baseline to 36 Months
Population: Two patients enrolled on the study and then withdrew early prior to treatment, therefore no data were collected before study termination.
Secondary
Turn Around Time for Systems Biology Analysis
No data displayed because Outcome Measure has zero total participants analyzed.
Time frame: Baseline to 36 Months
Population: Two patients enrolled on the study and then withdrew early prior to treatment, therefore no data were collected before study termination.