The Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Metastatic Breast Cancer Patients Previously Responsive to Hormonal Therapy: A Phase II Trial
19 Years
80 Years
Female
Metastatic Breast Cancer
Trial Information
The Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Metastatic Breast Cancer Patients Previously Responsive to Hormonal Therapy: A Phase II Trial
This is a single institution, open-label study designed to evaluate safety and efficacy of
Avastin (Bevacizumab) combined with an endocrine agent in patients with estrogen and/or
progesterone receptor positive metastatic breast carcinoma who have acquired resistance to
at least one hormonal agent. Patients will be treated with the same hormonal agent that was
used previously assuming that the patient had a partial or complete response (for at least 6
months) followed by a clear disease progression using the Response Evaluation Criteria in
solid Tumors (RECIST Criteria). Patients with stable disease for a prolonged time (for at
least 6 months) will be also eligible to enter in the trial. Patients who have not had
interval studies to evaluate disease response will be considered eligible if they have
remained clinically stable (i.e. stable PS, no increasing pain) and on the same hormone for
at least 6 months, and now they have signs and symptoms of clinical progression (i.e.
elevated tumor markers, increasing bone pain, worsening performance status). Patients must
have histologically confirmed measurable and/or evaluable metastatic breast cancer with
positive estrogen and/or progesterone receptors. Patients can have up to an 8-12 week break
in therapy (discontinuation of hormonal therapy) and still remain eligible for the study as
long as the documentation of disease progression is determined before the 8-12 week break in
hormonal therapy.
The type and dose of the hormonal agent that will be used in this trial will be the same one
that the patient used before progression. Hormonal therapy may include any estrogen
deprivation reagent such as Tamoxifen, Anastrazole, Exemestane, Letrozole, or Fulvestrant.
All patients will receive Avastin (Bevacizumab) 15 mg/kg IV every three weeks. Based on
statistical evaluations, 30 patients will be enrolled. The first evaluation of efficacy
will be done at week 6; patients with objective response or stable disease will continue
therapy with re-staging every 6 weeks until evidence of disease progression. Patients with
progression of disease will be taken off study (see appendix A). PET scan will be done at
baseline and only in the first evaluation (6 weeks) to obtain early "metabolic response
data" that will be correlated with objective response and time to disease progression (PET
data on week 6 will not be used to evaluate response and to make therapeutic decisions).
PET "metabolic response" will be defined as a >20% reduction in SUV. Safety will be
assessed by the recording of adverse events, serious adverse events, laboratory test
results, and changes in vital signs. A positive response to Avastin (Bevacizumab) (reversal
of hormonal resistance) will be defined as an objective response or stable disease of ≥ 3
months duration. All concomitant medication must be documented. Additionally, any
diagnostic, therapeutic or surgical procedure performed during the study period, should be
recorded including the date, indication, description of the procedure(s) and any clinical
findings.
Inclusion Criteria:
- Patients must have cytologically or histologically proven breast cancer which is
estrogen receptor or progesterone receptor positive and is locally advanced and /or
metastatic.
- Give written informed consent prior to study specific screening procedures, with the
understanding that the patient has the right to withdraw from the study at any time,
without prejudice (Appendix E).
- Be female and greater than or equal to 19 years of age (age limit required by the
State of Alabama). Women of childbearing potential must have a negative pregnancy
test and must be willing to consent to using effective contraception while on
treatment and for a reasonable period thereafter. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
- Be ambulatory (outpatient) and have an ECOG PS <2 (Appendix B).
- Previous treatment: Patients must have responded to first or second line hormonal
therapy (Partial and complete response greater than 6 months using RECIST criteria.
Patients with stable disease for more than 6 months will be eligible) and became
resistant to the hormonal agent. They must remain on the current hormone therapy to
which they initially responded but now are resistant.
- Clear documentation of acquired hormonal resistance.
- Evaluable disease will be considered eligible, but measurable disease according to
RECIST criteria will be preferable (Appendix C). The target lesion(s) must not have
been previously irradiated (newly arising lesions in previously irradiated areas are
acceptable).
- Patients must have adequate organ and marrow function as defined as follows: absolute
neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3, total
bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, transaminases (AST, ALT) may be up
to 2.5 x institutional upper limit of normal for patients with no liver metastases
and up to 5 x institutional upper normal limit for patients with documented liver
metastases. In addition < 1 gr of protein in 24 hr urine collection and urine
protein/creatinine ratio < 1.0
- Prior chemotherapy does not exclude patients from study as long as the current
therapy was hormonal therapy alone.
- Patients with de novo hormone therapy resistance will not be eligible.
- No life threatening parenchymal disease or rapidly progressing disease warranting
cytotoxic chemotherapy.
- No history of brain metastases.
- No history of thrombosis during the previous year, including transient ischemic
attack.
- Hypertension must be controlled (< 150/100 mmHg).
- Ejection Fraction > 50%.
Exclusion Criteria:
- Patients who are "de novo" resistant to hormone therapy.
- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than this Genentech-sponsored
bevacizumab cancer study.
- Blood pressure of >150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction within 6 months
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- History of a bleeding disorder
- Presence of central nervous system or brain metastases
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 0
- Pregnant (positive pregnancy test) or lactating
- Urine protein: creatinine ratio greater than or equal to 1.0 at screening. Patients
demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to
study entry will not participate in the trial.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0
- Serious, non-healing wound, ulcer, or bone fracture
- Unwilling or unable to comply with the protocol for the duration of the study.
- Psychiatric illness/social situations that would limit compliance with study
requirements.
- Previously radiated area(s) must not be the only site of disease.
- History of another malignancy within the last five years except cured basal cell
carcinoma of skin and carcinoma in-situ of uterine cervix.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression Free Survival (PFS)
Outcome Description:
Progression free survival is defined as time from date of randomization until the date of first documented disease progression or date of death from any cause, whichever occurs first.
Outcome Time Frame:
Every 6 weeks until disease progression
Safety Issue:
Yes
Principal Investigator
Carla Falkson, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Alabama at Birmingham
Authority:
United States: Food and Drug Administration
Study ID:
F050103001
NCT ID:
NCT00240071
Start Date:
October 2005
Completion Date:
April 2011
Related Keywords:
- Metastatic Breast Cancer
- Breast cancer
- Metastatic breast cancer
- Hormonal therapy
- Bevacizumab
- Breast Neoplasms
Name | Location |
|---|---|
| University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
