Metastatic Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
Conditions
Brief summary
This phase II trial is studying how well VEGF Trap works in treating patients with metastatic breast cancer. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor
Detailed description
PRIMARY OBJECTIVES: I. Assess the antitumor activity of VEGF Trap, in terms of tumor response rate, in patients with metastatic breast cancer who have received =\< 2 prior chemotherapy regimens for metastatic disease, including a taxane and/or anthracycline. II. Assess the 6-month progression-free survival rate in patients treated with VEGF Trap. SECONDARY OBJECTIVES: I. Describe the adverse event profile (grade using the NCI CTCAE version 3.0) of VEGF Trap in these patients. II. Describe the progression-free survival times in patients treated with VEGF Trap. III. Describe the overall survival of patients treated with VEGF Trap. IV. Describe the duration of response in patients treated with VEGF Trap. OUTLINE: This is a multicenter study. Patients receive VEGF Trap IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
Interventions
BIOLOGICALziv-aflibercept
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the breast * Clinical evidence of metastatic disease * No more than 2 prior chemotherapy regimens for metastatic disease * Prior neoadjuvant or adjuvant chemotherapy allowed\* * At least 1 prior regimen (in any setting) must have included a taxane and/or an anthracycline * Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured per RECIST criteria * No nonmeasurable disease, defined as all other lesions, including small lesions(longest diameter \< 20 mm) and truly nonmeasurable lesions, including the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural/pericardial effusion * Inflammatory breast disease * Lymphangitis cutis/pulmonis * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Patients with HER2-positive tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization \[FISH\]) must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen in either the adjuvant or metastatic setting, unless there was a contraindication * No known CNS metastases * No evidence of leptomeningeal involvement * Hormone receptor status not specified * Male or female * Menopausal status not specified * ECOG performance status 0-1 * Life expectancy \> 3 months * WBC ≥ 3,000/mm³ * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 75,000/mm³ * Hemoglobin \> 8.0 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * AST and ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN * Urine protein:creatinine ratio \< 1 OR urine protein \< 500 mg by 24-hour urine collection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after completion of study treatment * No significant traumatic injury within the past 4 weeks * No history of allergy or hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, drug product excipients, or agents chemically or biologically similar to VEGF Trap * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days * No nonhealing wound, fracture, or ulcer * No stage III or IV invasive, nonbreast malignancy within the past 5 years * No history of lung carcinoma of squamous cell type * No clinically significant cardiovascular disease, including any of the following: * Cerebrovascular accident or stroke within the past 6 months * Uncontrolled hypertension, defined as blood pressure (BP) \> 150/100 mm Hg OR systolic BP \> 180 mm Hg if diastolic blood pressure \< 90 mm Hg on ≥ 2 separate occasions within the past 3 months * Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months * New York Heart Association class III or IV cardiovascular disease * Serious cardiac arrhythmia requiring medication * Peripheral vascular disease ≥ grade 2 within the past 6 months * Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months * No evidence of bleeding diathesis or uncontrolled coagulopathy * No active, unresolved infection * No serious concurrent medical condition that would preclude study participation * No other condition or circumstance that would preclude compliance with study requirements * See Disease Characteristics * Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed * No prior bevacizumab * More than 4 weeks since prior chemotherapy, endocrine therapy, experimental drug therapy, or immunotherapy and recovered * More than 4 weeks since prior major surgery or open biopsy * More than 7 days since prior core biopsy * More than 2 weeks since prior radiotherapy, except if to a nontarget lesion only * Prior radiotherapy to a target lesion allowed only if there has been clear progression of the lesion since radiotherapy was completed * Prior single-dose palliative radiotherapy within the past 2 weeks allowed * No concurrent major surgery * No concurrent trastuzumab * Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR \> 1.5 allowed provided the following criteria are met: * INR in-range (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices) * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent participation in another investigational clinical trial * No other concurrent chemotherapeutic agents, endocrine therapy, biologic agents, radiotherapy, or other nonprotocol antitumor therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Confirmed Tumor Response | Up to 5 years | Confirmed tumor response was defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on 2 consecutive evaluations at least 8 weeks apart. |
| Proportion of Patients Receiving Vascular Endothelial Growth Factor (VEGF) Trap With 6-month Progression-free Survival | 6 months | The 6-month progression free survival rate was defined as the proportion of efficacy-evaluable patients on study treatment and progression-free 6 months from registration. Patients who died without documentation of progression will be considered to have progressed on the date of their death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Time from registration to disease progression or death (up to 5 years) | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who died without documentation of progression being considered to have progressed on the date of their death. |
| Overall Survival | Time from registration to death or last follow up (up to 5 years) | Overall survival time was defined as the number of months from registration to the date of death or last follow-up |
| Median Duration of Response | Up to 5 years | Duration of response was defined as for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response or partial response to the date progression is documented. |
| Number of Participant With Previous Treatment of Anti-HER2 With Cardiac Events | Up to 5 years | — |
Countries
United States
Participant flow
Recruitment details
Twenty-one women were enrolled during the first stage of the study between January 2007 and March 2008.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ziv-afibercept) Patients receive VEGF Trap IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Refusal of further treatment | 2 |
Baseline characteristics
| Characteristic | Treatment (Ziv-afibercept) |
|---|---|
| Age, Continuous | 58 years |
| Cell type Comedo | 1 Participants |
| Cell type Infiltrating ductal | 16 Participants |
| Cell type Infiltrating ductal and comedo | 1 Participants |
| Cell type Infiltrating lobular | 1 Participants |
| Cell type Inflammatory | 1 Participants |
| Cell type Missing | 1 Participants |
| Dominant Disease Nonvisceral | 6 Participants |
| Dominant Disease Visceral | 15 Participants |
| ECOG Performance Score 0-Fully active | 14 Participants |
| ECOG Performance Score 1-Ambulatory, restricted strenuous activity | 7 Participants |
| Estrogen Receptor (ER) Result Negative | 12 Participants |
| Estrogen Receptor (ER) Result Positive | 9 Participants |
| Human epidermal growth factor receptor 2 (HER2) Result HER2 testing not done | 3 Participants |
| Human epidermal growth factor receptor 2 (HER2) Result Negative | 14 Participants |
| Human epidermal growth factor receptor 2 (HER2) Result Positive | 4 Participants |
| Number of Previous Chemotherapy Regimens 0 | 3 Participants |
| Number of Previous Chemotherapy Regimens 1 | 11 Participants |
| Number of Previous Chemotherapy Regimens 2 | 7 Participants |
| Previous Hormonal Therapy No | 12 Participants |
| Previous Hormonal Therapy Yes | 9 Participants |
| Previous (Neo) Adjuvant Chemotherapy No | 8 Participants |
| Previous (Neo) Adjuvant Chemotherapy Yes | 13 Participants |
| Previous Trastuzumab No | 16 Participants |
| Previous Trastuzumab Yes | 5 Participants |
| Prior Anthracyclines No | 6 Participants |
| Prior Anthracyclines Yes | 15 Participants |
| Prior Taxanes No | 2 Participants |
| Prior Taxanes Yes | 19 Participants |
| Progesterone Receptor (PR) Result Negative | 16 Participants |
| Progesterone Receptor (PR) Result Positive | 5 Participants |
| Region of Enrollment United States | 21 participants |
| Sex/Gender, Customized Female | 21 participants |
| Visceral Disease Site Abodomen | 1 Participants |
| Visceral Disease Site Liver | 7 Participants |
| Visceral Disease Site Lung | 7 Participants |
| Visceral Disease Site Other | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 10 / 21 |
Outcome results
Primary
Proportion of Patients Receiving Vascular Endothelial Growth Factor (VEGF) Trap With 6-month Progression-free Survival
The 6-month progression free survival rate was defined as the proportion of efficacy-evaluable patients on study treatment and progression-free 6 months from registration. Patients who died without documentation of progression will be considered to have progressed on the date of their death.
Time frame: 6 months
Population: All participants who have met the eligibility criteria, who have signed a consent form and have begun treatment were evaluable for response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ziv-afibercept) | Proportion of Patients Receiving Vascular Endothelial Growth Factor (VEGF) Trap With 6-month Progression-free Survival | 2 Participants |
Primary
Proportion of Patients With Confirmed Tumor Response
Confirmed tumor response was defined as the total number of efficacy-evaluable patients who achieved a complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria on 2 consecutive evaluations at least 8 weeks apart.
Time frame: Up to 5 years
Population: All participants who have met the eligibility criteria, who have signed a consent form and have begun treatment were evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Ziv-afibercept) | Proportion of Patients With Confirmed Tumor Response | Confirmed tumor partial response | 1 Participants |
| Treatment (Ziv-afibercept) | Proportion of Patients With Confirmed Tumor Response | No Confirmed reponse | 20 Participants |
Secondary
Median Duration of Response
Duration of response was defined as for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response or partial response to the date progression is documented.
Time frame: Up to 5 years
Population: Analysis population included only patients who have achieved a confirmed tumor response. The duration of response of 4.6 months is reported from one patient.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ziv-afibercept) | Median Duration of Response | 4.6 Months |
Secondary
Number of Participant With Previous Treatment of Anti-HER2 With Cardiac Events
Time frame: Up to 5 years
Population: All participants who have received previous treatment with anti-HER2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Ziv-afibercept) | Number of Participant With Previous Treatment of Anti-HER2 With Cardiac Events | 1 Participants |
Secondary
Overall Survival
Overall survival time was defined as the number of months from registration to the date of death or last follow-up
Time frame: Time from registration to death or last follow up (up to 5 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ziv-afibercept) | Overall Survival | 12.7 Months |
Secondary
Progression Free Survival
Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who died without documentation of progression being considered to have progressed on the date of their death.
Time frame: Time from registration to disease progression or death (up to 5 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ziv-afibercept) | Progression Free Survival | 2.7 Months |