Metastatic Breast Cancer
Conditions
Keywords
Metastatic Breast Cancer, Molecular profiling
Brief summary
The purpose of this study is to determine the response rate, that is the % of patients with non-progression of their metastatic breast cancer after 4 months on treatment that was selected by molecular testing and proteomics.
Detailed description
To determine the percent of patients with refractory breast cancer where molecular profiling and RPMA-based protein pathway activation analysis of their tumor, can change the clinical course of their disease (i.e. produce a Growth Modulation Index (GMI) ≥1.3). The GMI is calculated as the ratio of Progression-free survival (PFS) under molecular profiling and RPMA analysis selected treatment to the time to progression (TTP) for the most recent regimen the patient has progressed on.
Interventions
DRUGApproved therapy will be assigned based on molecular profile and RPMA results
treatment will be assigned based on IHC\< FISH, DNA microarray and RPMA results
Sponsors
Side-Out Foundation
Translational Drug Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a life expectancy of greater than 3 months * metastatic breast cancer, with measurable or evaluable non-measurable disease * Have progressed on at least 3 prior chemotherapeutic or biological regimens * Be defined as refractory to the last line of therapy according to the following criteria: Documented disease progression under the last treatment or within two months of the last treatment dosing AND Have received ≥ 30 days of the last treatment AND Have discontinued for progression by RECIST 1.1 criteria * ≥18 years of age * ECOG 0-1 * willing to undergo a biopsy or surgical procedure to obtain tissue * Must have been off their prior regimen for ≥ 3 weeks or 5 x half life of drug * Have adequate organ and bone marrow function as defined below: * Female patients of child-bearing potential must have a negative pregnancy test and agree to use at least one form of contraception during the study and for at least one month after treatment discontinuation. For the purposes of this study, child-bearing potential is defined as: all female patients unless they are post-menopausal for at least one year or are surgically sterile * Male patients must use a form of barrier contraception approved by the Investigator during the study and for at least one month after treatment discontinuation.
Exclusion criteria
* Tumor biopsy intended for use in the current study which was performed more than 2 months prior * Frozen material is not available/obtained * Metastatic lesion is not accessible to biopsy * Patients with \> 6 months treatment under the last line of therapy * Patients with symptomatic CNS metastasis. Patients with a history of CNS metastases who have been treated must be stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for ≥ 2 weeks prior to enrollment * Any previous history of another malignancy (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of study entry * Uncontrolled concurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, psychiatric illness, or situations that would limit compliance with the study requirements or the ability to willingly give written informed consent * Known HIV, HBV, HCV infection * Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Growth Modulation Index (GMI) Greater Than or Equal to 1.3 | 6-20 weeks | The primary objective was to determine the % of patients with refractory breast cancer where MMP-informed selection of approved cancer therapies could change the clinical course of their disease to produce a Growth Modulation Index (GMI) greater than 1.3. The GMI was calculated as the PFS with MMP-selected therapy/time to progression (TTP) on last prior therapy. A GMI of 1.3 was selected because 30% or greater improvement in PFS with MMP-selected therapy compared to previous TTP would be considered clinically meaningful. |
Countries
United States
Participant flow
Recruitment details
The open-label multicenter pilot study accrued patients between March 2010 and June 2012. Three Oncology Practices contributed patients to the study.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Intervention Details:
Drug: (will be assigned based on molecular profile and RPMA)
treatment will be assigned based on IHC\< FISH, DNA microarray and RPMA results | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Intervention |
|---|---|
| Age, Customized age | 58 years |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants |
| Region of Enrollment United States | 25 participants |
| Sex/Gender, Customized Female | 25 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Growth Modulation Index (GMI) Greater Than or Equal to 1.3
The primary objective was to determine the % of patients with refractory breast cancer where MMP-informed selection of approved cancer therapies could change the clinical course of their disease to produce a Growth Modulation Index (GMI) greater than 1.3. The GMI was calculated as the PFS with MMP-selected therapy/time to progression (TTP) on last prior therapy. A GMI of 1.3 was selected because 30% or greater improvement in PFS with MMP-selected therapy compared to previous TTP would be considered clinically meaningful.
Time frame: 6-20 weeks
Population: A total of 28 patients were enrolled and underwent tumor biopsy for the purposes of this study. 25/28 patients were treated on study with the MMP-selected treatment and were evaluable for the primary end point of GMI.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Growth Modulation Index (GMI) Greater Than or Equal to 1.3 | 25 Participants |