Breast Cancer
Conditions
Keywords
Breast Cancer, Metastatic, PRO Onc Assay, FISH Testing, HER Negative, HER Overexpression, HER Activation
Brief summary
This trial will evaluate the clinical significance of the PRO Onc assay and will assess the efficacy of HER2-targeted therapy in patients with HER2-negative breast cancer who have been identified as having HER2 overexpression/activation by the PRO Onc Assay.
Detailed description
This two-part trial is designed to evaluate the clinical significance of the PRO Onc assay when used in patients with metastatic HER2-negative breast cancer. The first part of this study will determine the incidence of HER overexpression/activation, as determined by the PRO Onc assay, in patients previously judged to have HER2-negative breast cancer by FISH analysis. Blood specimens will be obtained from patients with HER2-negative breast cancer; CTCs will then be isolated and tested for HER2 overexpression/activation using the PRO Onc Assay. When clinically indicated, fine needle aspiration biopsy will also be obtained and submitted for the PRO Onc Assay. If the incidence of HER2 overexpression/activation, as determined by the PRO Onc Assay, is \>10%, the study will proceed to Part 2. Part 2 of this study will assess the efficacy of HER2-targeted therapy in a group of patients with HER2-negative breast cancer who are identified as having HER2 overexpression/activation by the PRO Onc Assay. Patients will be treated with either trastuzumab or pertuzumab. Patients who progress during the first 8 weeks will have HER2-targeted treatment discontinued and will be removed from study. After 8 weeks, patients who have stable disease will be allowed to add chemotherapy to HER2-targeted therapy. Patients who have an objective response to single-agent, HER2-targeted therapy after 8 weeks will continue single-agent therapy.
Interventions
PROCEDUREPRO Onc Assay and Treatment
Patients with HER2-negative metastatic breast cancer will be identified, and blood specimens will be obtained from each participant. The PRO Onc Assay will be performed on CTCs isolated from these specimens. When clinically indicated, fine needle aspiration biopsy will also be obtained and submitted for the PRO Onc Assay.
DRUGTrastuzumab
8 mg/kg IV loading dose, followed by 6 mg /kg IV every 3 weeks until progressive disease or unacceptable toxicity with evaluations performed every 8 weeks
DRUGPertuzumab
840 mg IV loading dose, followed by 420 IV every 3 weeks until progressive disease or unacceptable toxicity with evaluations performed every 8 weeks
Sponsors
Prometheus Laboratories
Genentech, Inc.
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part I 1. Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.) 2. Patients should be currently receiving chemotherapy, or scheduled to start chemotherapy (second-line or subsequent), for HER2-negative metastatic breast cancer. 3. To begin protocol treatment, patients must have progressed after at least 1 previous chemotherapy regimen for metastatic breast cancer. 4. Patients who are ER/PR positive or negative are eligible. ER/PR positive patients should be refractory to hormonal therapy, or not good candidates for hormonal therapy due to clinical features. 5. ECOG performance status of 0, 1 or 2. 6. Adequate recovery from recent surgery; ≥ 1 week must have elapsed from the time of a minor surgery; ≥ 4 weeks must have elapsed from the time of a major surgery. 7. Patients must have measurable disease per RECIST criteria. 8. Laboratory values as follows: Absolute neutrophil count (ANC) ≥1500/μL Hemoglobin (Hgb) ≥10 g/dL Platelets ≥100,000/L AST or ALT and alkaline phosphatase (ALP) must be \<2.5 x ULN, or \<5 x ULN in patients with liver metastases. Total bilirubin \<1.5 x the institutional ULN Serum creatinine \<1.5 x institutional ULN or calculated creatinine clearance ≥45 mL/min Patients from Part 1 who have HER2 overexpression/activation identified by the PRO Onc Assay may enter the treatment portion of Part 2, if they meet all Part 2 eligibility criteria. 9. Life expectancy of ≥ 12 weeks. 10. Patient must be accessible for treatment and follow-up. 11. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry. Part II 1. Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.) 2. Patients should be currently receiving chemotherapy, or scheduled to start chemotherapy, for HER2-negative metastatic breast cancer. 3. Patients who are ER/PR positive or negative are eligible. ER/PR positive patients should be refractory to hormonal therapy, or not good candidates for hormonal therapy due to clinical features. 4. ECOG performance status of 0, 1 or 2. 5. Adequate recovery from recent surgery; ≥ 1 week must have elapsed from the time of a minor surgery; ≥ 4 weeks must have elapsed from the time of a major surgery. 6. Patients must have measurable disease per RECIST criteria. 7. Laboratory values as follows: * Absolute neutrophil count (ANC) ≥1500/μL * Hemoglobin (Hgb) ≥10 g/dL * Platelets ≥100,000/uL * AST or ALT and alkaline phosphatase (ALP) must be \<2.5 x ULN, or \<5 x ULN in patients with liver metastases. * Total bilirubin \<1.5 x the institutional ULN * Serum creatinine \<1.5 x institutional ULN or calculated creatinine clearance ≥45 mL/min 8. Life expectancy of ≥ 12 weeks. 9. Patient must be accessible for treatment and follow-up. 10. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry. 11. Patients who are eligible for HER2-targeted treatment will begin this treatment at the first time a treatment change is necessary (i.e. at the next progression of metastatic breast cancer). This may occur immediately after PRO Onc assay results are received, or may be several months later, for patients responding well to their current chemotherapy. 12. Patients must continue to meet all inclusion and
Exclusion criteria
for the Part 2 screening population at the time they are ready to start HER2-targeted treatment. 13. Ejection fraction ≥ 50%, as measured by echocardiogram (ECHO) or MUGA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part II: Objective Response Rate of HER2-negative Metastatic Breast Cancer (by FISH Testing) | 18 months | The percentage of HER2-negative metastatic breast cancer (MBC) patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression/activation as detected by PRO Onc Assay. |
| Part II: Objective Response Rate of Trastuzumab Therapy | 18 months | The percentage of patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression as identified by the PRO Onc Assay. |
| Part II: Objective Response Rate of Pertuzumab Therapy | 18 months | The percentage of patients with HER2 activation (no overexpression) as identified by the PRO Onc Assay who experience an objective benefit from treatment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay | 12 months | Includes patients with HER2-negative metastatic breast cancer (MBC) as determined by FISH testing. |
| Part I: The Incidence of Isolation of Circulating Tumor Cells (CTCs) From Blood Specimens | 12 months | Percentage of HER2-negative MBC patients (identified by FISH testing) having CTCs present in blood specimens. |
Countries
United States
Participant flow
Recruitment details
Pts with HER2-negative, metastatic breast cancer were enrolled. Blood was collected to perform the PRO Onc Circulating Tumor Cell (CTC). Pts without CTCs present were taken off-study. Following the assay, pts without detected HER2 overexpression/activation were taken off-study. Of the remaining pts, those FISH-positive for HER2 came off-study.
Participants by arm
| Arm | Count |
|---|---|
| Patients Treated Patients who received study treatment | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Patients Enrolled and Blood Collected | Patients without circulating tumor cells | 57 |
| Patients Evaluated by PRO Onc Assay | Patients with no HER2 abnormality | 202 |
Baseline characteristics
| Characteristic | Patients Treated |
|---|---|
| Age, Continuous | 65 years |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 14 |
| serious Total, serious adverse events | 5 / 14 |
Outcome results
Primary
Part II: Objective Response Rate of HER2-negative Metastatic Breast Cancer (by FISH Testing)
The percentage of HER2-negative metastatic breast cancer (MBC) patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression/activation as detected by PRO Onc Assay.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Evaluated by PRO Onc Assay | Part II: Objective Response Rate of HER2-negative Metastatic Breast Cancer (by FISH Testing) | 7 percentage of participants |
Primary
Part II: Objective Response Rate of Pertuzumab Therapy
The percentage of patients with HER2 activation (no overexpression) as identified by the PRO Onc Assay who experience an objective benefit from treatment, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 months
Population: Includes patients with only HER2 activation (no overexpression) as detected by the PRO Onc Assay
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Evaluated by PRO Onc Assay | Part II: Objective Response Rate of Pertuzumab Therapy | 0 percentage of participants |
Primary
Part II: Objective Response Rate of Trastuzumab Therapy
The percentage of patients having an objective benefit from treatment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Includes patients with HER2 overexpression as identified by the PRO Onc Assay.
Time frame: 18 months
Population: Includes patients with HER2 overexpression detected by the PRO Onc Assay
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Evaluated by PRO Onc Assay | Part II: Objective Response Rate of Trastuzumab Therapy | 10 percentage of participants |
Secondary
Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay
Includes patients with HER2-negative metastatic breast cancer (MBC) as determined by FISH testing.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Patients Evaluated by PRO Onc Assay | Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay | HER2 activated | 10 participants |
| All Patients Evaluated by PRO Onc Assay | Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay | HER2 overexpressed | 11 participants |
| All Patients Evaluated by PRO Onc Assay | Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay | HER2 overexpressed and activated | 3 participants |
| All Patients Evaluated by PRO Onc Assay | Part 1: The Incidence of HER2 Overexpression/Activation as Measured by the PRO Onc Assay | No HER2 overexpression/activation detected | 202 participants |
Secondary
Part I: The Incidence of Isolation of Circulating Tumor Cells (CTCs) From Blood Specimens
Percentage of HER2-negative MBC patients (identified by FISH testing) having CTCs present in blood specimens.
Time frame: 12 months
Population: Includes all patients with blood drawn and analyzed for CTCs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Evaluated by PRO Onc Assay | Part I: The Incidence of Isolation of Circulating Tumor Cells (CTCs) From Blood Specimens | 80 percentage of participants |