Breast Cancer Clinical Trial
Official title:
A Phase II Trial of Neoadjuvant Arimidex With or Without Faslodex in Postmenopausal Women With Hormone Receptor Positive Breast Cancer
Over the last 3 decades, a steady shift has occurred in the management of breast cancer.
Because it was traditionally viewed as a local disease, many advocated the use of radical
surgery to achieve maximum survival benefit. This view has been slowly replaced by a broader
biologic view that recognizes the often systemic nature of breast cancer, even when it
appears to be localized to the breast. Results from randomized clinical trials have
demonstrated that less extensive surgery, or lumpectomy plus radiation therapy, are optimal
for local management of early breast cancer. In addition to the less radical approach to
surgical treatment of breast cancer, other randomized clinical trials have established the
value of postoperative systemic therapy in improving overall survival by eradicating
micrometastatic disease, the major cause of mortality from breast cancer. Despite the
well-documented benefits of adjuvant systemic therapy, it is not effective in preventing
death from breast cancer in all patients who are candidates for such treatment. The worth of
such therapy can only be judged in retrospect upon disease relapse, a time when breast cancer
is nearly always incurable. Currently, there are few reliable methods to predict the success
or failure of a particular postoperative treatment modality, and better ways to predict and
optimize outcome are needed.
Combination endocrine therapy: Using endocrine agents with different mechanisms of action
together has the potential advantage of more effectively blocking ER signaling, thus
improving the efficacy of such agents against breast cancer. In the past, attempts to combine
endocrine agents for ER-positive breast cancer have had mixed results, depending on the
setting and the patient population studied.
Endocrine agents without any agonist effect could potentially be used in combination with
aromatase inhibitors, under the rationale that the combination would maximally blockade
estrogen receptor signaling, thus potentially improving the antitumor effect. Fulvestrant
(FASLODEX) is a pure estrogen antagonist with no known agonist effect; thus, it has the
potential to provide additional benefit when combined with an aromatase inhibitor. This
concept provides the rationale for using the combination of anastrazole and fulvestrant in
this study.
Purpose and Objectives
The primary objective of this study is to determine if ER-targeted therapy, ARIMIDEX and
FASLODEX, used in combination is superior to ARMIDEX alone in hormone receptor positive
breast cancer.
Primary study objective 1. To determine the efficacy of primary breast cancer, as measured by
decrease in proliferation (KI67), to the combination of ARIMIDEX, and FASLODEX at high dose
Secondary study objectives 1. To study molecular changes in response to treatment. 2. To
correlate changes in Ki67 with clinical response 3. To determine the pathologic response
rate. 4. To assess the tolerability and safety of the combination regimen.
This is a phase II randomized multi-center study. As indicated in the study design schema
found in the protocol document attached to Section S, patients will be initially randomized
to receive ARIMIDEX, or ARIMIDEX+FASLODEX (high dose) for 16 weeks (112 days). A
computer-generated randomization scheme will be generated by the study statistician at the
Breast Center, Baylor College of Medicine. A 1:1 randomization scheme using permuted blocks
will be employed. Randomization will be centralized at the Breast Center, Baylor College of
Medicine and accomplished via access to a secure web-based procedure that is currently being
implemented in our other multi-center clinical trials. Enrollment, eligibility, and
randomization information will be stored in an Oracle database on the Breast Center's Sun
server and will be accessible only through secure web-based applications. Communication with
the pharmacy will be handled by email which will contain only patient identification number
and initials and by FAX or hardcopy. The hardcopy will be used by physicians to send to the
pharmacy a signed computer-generated pharmacy order to legally dispense study drug.
Within 30 days prior to randomization subjects will sign the study consent form, and have a
history and physical exam, including all concurrent medications. Blood will be drawn for CBC,
platelets, serum chemistries, BUN, creatinine, and liver function tests. If necessary to
determine menopausal status FSH, LH and serum estradiol will be obtained. An EKG, CXR PA and
lateral will be performed and a bilateral mammogram and US of primary breast cancer will be
done within 90 days of randomization. Subjects will then be randomized to receive either
ARIMIDEX 1 mg po q day (Group A), or ARIMIDEX 1 mg po q day and FASLODEX 500 mg IM, day 1,
day 14, day 28 and thereafter once every 28 days (Group B). Study medications will be
dispensed within 60 days of randomization. On day 28, subjects will be evaluated for side
effects and a second breast core biopsy will be obtained. Evaluation for tumor response and
tolerability of the regimen will be evaluated every 28 days in outpatient clinic visits. ALL
treatment will continue until day 112 when patients with a clinical response or stable
disease will receive appropriate surgical resection. If the tumor is unresectable on day 112,
a core needle biopsy will be done. The surgical specimen will be obtained for further
molecular analysis. After surgery, patients will be off study and will receive additional
breast cancer therapy at the discretion of their treating physician. Patients who develop
progressive disease on protocol will be taken off study and offered alternative treatment.
All patients will have a safety follow-up 1 month after the surgery (or the alternative core
biopsy).
Treatment will be administered on outpatient basis. After the baseline breast biopsy,
patients will be randomized to receive ARIMIDEX 1mg po q day (group A), or ARIMIDEX 1mg po q
day with FASLODEX 500 mg day 1, day 14, day 28, and thereafter every 28 days (Group B). After
28 days a second biopsy will be obtained in all patients. All patients will continue on the
same randomized treatment for the total duration of the study of 112 days till the day before
surgery. No investigational or commercial agents or therapies other than those described
below may be administered with the intent to treat the patient's malignancy.
Study Visit Procedures: Pre-Study Procedures will include the following: informed consent,
breast biopsy, demographics, medical history, concurrent medication list, physical exam,
blood draw, bidimensional tumor measurement, bilateral mammogram, primary breast ultrasound
and chest x-ray.
Day 1 procedures will include the following: study drug administration, clinic visit.
Day 14 procedures will include the following (group B only) study drug injection and clinic
visit.
Day 28 procedures will include the following (group B only) study drug injection. Both group
A and B, breast biopsy, concurrent medication list, physical exam, blood draw, clinic visit,
adverse events evaluation, bidimensional tumor measurement.
Day 56 procedures will include the following (group B only) study drug injection. Both group
A and B, concurrent medication list, physical exam, blood draw, adverse events evaluation,
clinic visit and bidimensional tumor measurement.
Day 84 procedures include (group B only) study drug injection. Both group A and B, concurrent
medication list, physical exam, blood draw, adverse event evaluation, clinic visit and
bidimensional tumor measurement.
Day 112 procedures include study drug administration, concurrent medication list, physical
exam, blood draw, adverse events evaluation, bidimensional tumor measurement, bilateral
mammogram, primary breast ultrasound and tumor resection.
Day 140 procedures include blood draw, clinic visit and safety evaluation for adverse events.
Duration of Therapy In the absence of treatment delays due to adverse events, treatment will
continue for 4 months or until one of the following criteria applies: Disease progression,
Intercurrent illness that prevents further administration of treatment, Unacceptable adverse
events(s), Patient decides to withdraw from the study, or General or specific changes in the
patient's condition render the patient unacceptable for further treatment in the judgment of
the investigator.
This protocol will close 6 months after the last patient is enrolled. Patients will receive
study medications from day 0 until day 111, which is the day before their planned surgery. On
day 140, patients will have a safety follow up visit and to determine the need for further
treatment after surgery.
Breast Core Biopsy All subjects will have a breast tumor core biopsy at the beginning of the
study, and a second biopsy after 2 weeks. Core needle biopsies are planned because they will
provide sufficient histologically evaluable tissue for the assays proposed in this study.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04681911 -
Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
|
Phase 2 | |
Terminated |
NCT04066790 -
Pyrotinib or Trastuzumab Plus Nab-paclitaxel as Neoadjuvant Therapy in HER2-positive Breast Cancer
|
Phase 2 | |
Completed |
NCT04890327 -
Web-based Family History Tool
|
N/A | |
Completed |
NCT03591848 -
Pilot Study of a Web-based Decision Aid for Young Women With Breast Cancer, During the Proposal for Preservation of Fertility
|
N/A | |
Recruiting |
NCT03954197 -
Evaluation of Priming Before in Vitro Maturation for Fertility Preservation in Breast Cancer Patients
|
N/A | |
Terminated |
NCT02202746 -
A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer
|
Phase 2 | |
Active, not recruiting |
NCT01472094 -
The Hurria Older PatiEnts (HOPE) With Breast Cancer Study
|
||
Recruiting |
NCT06057636 -
Hypnosis for Pain in Black Women With Advanced Breast Cancer: A Feasibility Study
|
N/A | |
Recruiting |
NCT06049446 -
Combining CEM and Magnetic Seed Localization of Non-Palpable Breast Tumors
|
||
Recruiting |
NCT05560334 -
A Single-Arm, Open, Exploratory Clinical Study of Pemigatinib in the Treatment of HER2-negative Advanced Breast Cancer Patients With FGFR Alterations
|
Phase 2 | |
Active, not recruiting |
NCT05501769 -
ARV-471 in Combination With Everolimus for the Treatment of Advanced or Metastatic ER+, HER2- Breast Cancer
|
Phase 1 | |
Recruiting |
NCT04631835 -
Phase I Study of the HS-10352 in Patients With Advanced Breast Cancer
|
Phase 1 | |
Completed |
NCT04307407 -
Exercise in Breast Cancer Survivors
|
N/A | |
Recruiting |
NCT03544762 -
Correlation of 16α-[18F]Fluoro-17β-estradiol PET Imaging With ESR1 Mutation
|
Phase 3 | |
Terminated |
NCT02482389 -
Study of Preoperative Boost Radiotherapy
|
N/A | |
Enrolling by invitation |
NCT00068003 -
Harvesting Cells for Experimental Cancer Treatments
|
||
Completed |
NCT00226967 -
Stress, Diurnal Cortisol, and Breast Cancer Survival
|
||
Recruiting |
NCT06006390 -
CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT06019325 -
Rhomboid Intercostal Plane Block on Chronic Pain Incidence and Acute Pain Scores After Mastectomy
|
N/A | |
Recruiting |
NCT06037954 -
A Study of Mental Health Care in People With Cancer
|
N/A |