Ignite Creation Date:
2024-05-05 @ 6:58 PM
Last Modification Date:
2024-10-26 @ 9:38 AM
Study NCT ID:
NCT00570323
Status:
COMPLETED
Last Update Posted:
2020-07-28
First Post:
2007-12-06
Brief Title:
Arimidex With or Without Faslodex In Postmenopausal Women With HR Positive Breast Cancer
Sponsor:
Mothaffar Rimawi
Organization:
Baylor Breast Care Center
Study Overview
Official Title:
A Phase II Trial of Neoadjuvant Arimidex With or Without Faslodex in Postmenopausal Women With Hormone Receptor Positive Breast Cancer
Status:
COMPLETED
Status Verified Date:
2020-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PACT001
Brief Summary:
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
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
Detailed Description:
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 ARIMIDEXFASLODEX 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 11 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 Centers 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 patients 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 eventss Patient decides to withdraw from the study or General or specific changes in the patients 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
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 ARIMIDEXFASLODEX 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 11 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 Centers 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 patients 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 eventss Patient decides to withdraw from the study or General or specific changes in the patients 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IRUSFULV0060 | OTHER | AstraZeneca | None |