Metastatic Breast Cancer
Conditions
Keywords
HER2 overexpressed, Metastatic Breast Cancer, Elderly
Brief summary
This is a phase II study that combines Trastuzumab with Pertuzumab to see how it works in women age greater than 60 who have been diagnosed with HER2/neu overexpressed locally advanced and/or metastatic breast carcinoma.
Detailed description
Currently available standard therapies for HER2 overexpressed metastatic breast cancers (MBC) include treatments with chemotherapy or hormonal therapy, alone or in combination with medications that target HER2 gene, such as Trastuzumab or Pertuzumab. This study will examine the effect of treating HER2 overexpressed MBC with the combination of Trastuzumab plus Pertuzumab, without hormonal or chemotherapy, as a first line treatment. If patients progress on this treatment, they will receive hormonal or chemotherapy in addition to the Trastuzumab plus Pertuzumab treatment. The objective is to see how the overall response rate for this treatment compares to other first line treatments in the same patient population.
Interventions
DRUGHormonal Therapy with Anastrozole and Fulvestrant
Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days
DRUGChemotherapy with Eribulin
Sponsors
Genentech, Inc.
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Women ≥60 Years of Age. 2. Histologically confirmed, locally advanced (T4 primary tumor and stage IIIB or IIIC disease) or metastatic breast cancer that progressed after treatment with standard treatment regimens in the adjuvant or neoadjuvant setting. 3. Prior treatment with trastuzumab and/or lapatinib in the neo-adjuvant or adjuvant setting is allowed but not required. Lapatininb has to be discontinued \> 21 days before the initiation of the T+P study treatments. 4. Up to 3 prior chemo regimens for treatment of metastatic disease are allowed as long as the study subject is acceptable for study treatment with chemo required on this study in cohort 2 at progression on T+P. 5. Patients may have had prior hormonal therapy with any hormonal agents as per section 3.1.5 of this protocol. 6. Zometa or denosumab can be continued as per standard of care as long as started before the study treatment is started. 7. HER2 positive breast cancer, as defined in Section 3.3 of this protocol 8. Must have measurable or evaluable disease according to RECIST 1.1 criteria. 9. Lab values obtained ≤7 days prior to registration as indicated in 3.1.9 of this protocol. 10. ECOG Performance Status (PS) of 0, 1 or 2. 11. LVEF at least 50% as determined by MUGA or ECHO. 12. Life expectancy \>3 months. 13. Written informed consent. 14. Willingness to return to study site for treatment and follow-up. 15. Normal QTc interval defined on EKG as QTc ≤ 440 msec. 16. Postmenopausal women defined in section 3.1.16 of this protocol.
Exclusion criteria
1. Stage III or IV cancer, other than breast cancer, in ≤5 years prior to registration. 2. Actively being treated for other malignancy. 3. New York Heart Association Class III or IV cardiovascular disease. 4. History of coronary heart failure (CHF) 5. Current use of drugs known to prolong the QTc interval including Class Ia and III antiarrhythmics or history of congenital long QTc syndrome. 6. Evidence of active brain metastasis including leptomeningeal involvement. 7. Major surgery, chemotherapy, hormonal or immunologic therapy ≤3 weeks prior to registration. 8. Radiotherapy ≤3 weeks prior to registration, except if to a non-target lesion only. 9. Prior treatment with Pertuzumab, Eribulin, Fulvestrant or Anastrozole. 10. Uncontrolled illness. 11. Co-morbid systemic illnesses or other severe concurrent disease. See section 3.2.11. 12. Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered. 13. Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive. 14. International normalized ratio (INR), activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \>1.5 × ULN (unless on anticoagulation medication) 15. Receipt of intravenous (IV) antibiotics for infection within 7 days prior to enrollment into the study. 16. Current chronic daily treatment with corticosteroids. See section 3.2.16 of this protocol. 17. Known hypersensitivity to any of the study treatments or to excipients of recombinant human or humanized antibodies. 18. History of receiving any investigational treatment within 28 days prior to enrollment into the study. 19. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in Patients | Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months | Defined as the total of complete response (CR) defined as a disappearance of all target lesions, partial response (PR) defined as \>= 30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) \>= 27 weeks among the total number of participants as defined by the Response Evaluation in Solid Tumors (RECIST) 1.1 response criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months | Progression Free Survival in treatment cohorts 1 and 2 as well as arms A and B from the time on study until progression of disease or death |
| Overall Survival (OS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, an average of 2 years. | Overall survival (OS) in treatment cohorts 1 and 2 as well as arms A and B from the time on study until death |
| Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 | Participants were followed during the study and for 30 days after completion of the study treatment, up to 12 months | the safety and tolerability of Trastuzumab and Pertuzumab alone and in combination with hormonal therapy or single agent chemotherapy. in HER2+ MBC patients |
| Quality of Life Via Patient-reported Outcomes | Duration of study, participants were followed every cycle up to 11 months. | quality of life and treatment side effects via patient-reported and investigator reported outcomes |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: T+P Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy)
Trastuzumab plus Pertuzumab | 2 |
| Cohort 2 - Arm A Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR +
Trastuzumab plus Pertuzumab
Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days | 0 |
| Cohort 2 - Arm B Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR -
Trastuzumab plus Pertuzumab
Chemotherapy with Eribulin | 0 |
| Total | 2 |
Baseline characteristics
| Characteristic | Cohort 1: T+P | Cohort 2 - Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White/ Non-Hispanic | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 2 participants | — | 2 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 0 / 0 | 2 / 2 |
| other Total, other adverse events | 2 / 2 | 0 / 0 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 0 | 0 / 2 |
Outcome results
Primary
Overall Response Rate (ORR) in Patients
Defined as the total of complete response (CR) defined as a disappearance of all target lesions, partial response (PR) defined as \>= 30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) \>= 27 weeks among the total number of participants as defined by the Response Evaluation in Solid Tumors (RECIST) 1.1 response criteria.
Time frame: Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months
Population: Participants started in Cohort 1: T+P Arm/Group and continued in Cohort 2 Arm B due to progressive disease
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: T+P | Overall Response Rate (ORR) in Patients | Complete Response (CR) | 0 Participants |
| Cohort 1: T+P | Overall Response Rate (ORR) in Patients | Partial Response (PR) | 1 Participants |
| Cohort 1: T+P | Overall Response Rate (ORR) in Patients | Stable Disease (SD) | 1 Participants |
| Cohort 2 - Arm B | Overall Response Rate (ORR) in Patients | Complete Response (CR) | 0 Participants |
| Cohort 2 - Arm B | Overall Response Rate (ORR) in Patients | Partial Response (PR) | 0 Participants |
| Cohort 2 - Arm B | Overall Response Rate (ORR) in Patients | Stable Disease (SD) | 2 Participants |
Secondary
Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0
the safety and tolerability of Trastuzumab and Pertuzumab alone and in combination with hormonal therapy or single agent chemotherapy. in HER2+ MBC patients
Time frame: Participants were followed during the study and for 30 days after completion of the study treatment, up to 12 months
Population: No participants were enrolled in Cohort 2- Arm A
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: T+P | Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 | participant 1 | 5 participants |
| Cohort 1: T+P | Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 | participant 2 | 5 participants |
| Cohort 2 - Arm B | Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 | participant 1 | 2 participants |
| Cohort 2 - Arm B | Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 | participant 2 | 8 participants |
Secondary
Overall Survival (OS)
Overall survival (OS) in treatment cohorts 1 and 2 as well as arms A and B from the time on study until death
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, an average of 2 years.
Population: Participants started in Cohort 1: T+P Arm/Group and continued in Cohort 2 Arm B due to progressive disease. The analysis below reflects Cohort 2 only
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 2 - Arm B | Overall Survival (OS) | Subject 1 | 25 Months |
| Cohort 2 - Arm B | Overall Survival (OS) | Subject 2 | 14 Months |
Secondary
Progression-free Survival (PFS)
Progression Free Survival in treatment cohorts 1 and 2 as well as arms A and B from the time on study until progression of disease or death
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months
Population: No participants were enrolled in Cohort 2- Arm A
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: T+P | Progression-free Survival (PFS) | Subject 1 | 6 weeks |
| Cohort 1: T+P | Progression-free Survival (PFS) | Subject 2 | 24 weeks |
| Cohort 2 - Arm B | Progression-free Survival (PFS) | Subject 1 | 12 weeks |
| Cohort 2 - Arm B | Progression-free Survival (PFS) | Subject 2 | 24 weeks |
Secondary
Quality of Life Via Patient-reported Outcomes
quality of life and treatment side effects via patient-reported and investigator reported outcomes
Time frame: Duration of study, participants were followed every cycle up to 11 months.
Population: Two patients were enrolled, no data was analyzed.