Ignite Creation Date:
2024-05-05 @ 10:45 PM
Last Modification Date:
2024-10-26 @ 10:23 AM
Study NCT ID:
NCT01176799
Status:
UNKNOWN
Last Update Posted:
2016-06-22
First Post:
2010-08-05
Brief Title:
Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
Sponsor:
National University Hospital Singapore
Organization:
National University Hospital Singapore
Study Overview
Official Title:
Phase II Randomized Study of Doxorubicin and Cyclophosphamide With or Without Intermittent Sunitinib in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor
Status:
UNKNOWN
Status Verified Date:
2016-06
Last Known Status:
RECRUITING
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:
None
Brief Summary:
This is a single-centre phase II randomized study of doxorubicin and cyclophosphamide AC with or without intermittent sunitinib in patients with measurable primary breast cancer who are receiving pre-operative chemotherapy
A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration
A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study Eligible patients will be randomized 11 to either arm A or arm B Patients will be stratified according to metastatic status metastatic vs non-metastatic and presence or absence of clinical T4 disease
Arm A Control arm
Doxorubicin 60mgm2 day 1 Cyclophosphamide 600mgm2 day1 every 3 weeks x 4 cycles
Arm B Experimental arm
Days -13 or -7 to day 0 total 7 or 14 days - oral sunitinib daily duration and dose as determined from the lead-in phase I study Cycle 1 day 1 - Cycle 1 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 2 day 1 - Cycle 2 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 3 day 1 - Cycle 3 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 4 day 1 - Cycle 4 AC 60600mgm2
DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject
Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1 and on days 1 and 15 of each subsequent cycle In addition patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC
A lead-in phase I study was built into this protocol to determine the dose and duration of sunitinib that may achieve the desired effects of normalizing tumor vasculature prior to chemotherapy administration
A total of 64 patients with measurable primary tumor will be enrolled for the Phase II part of the study Eligible patients will be randomized 11 to either arm A or arm B Patients will be stratified according to metastatic status metastatic vs non-metastatic and presence or absence of clinical T4 disease
Arm A Control arm
Doxorubicin 60mgm2 day 1 Cyclophosphamide 600mgm2 day1 every 3 weeks x 4 cycles
Arm B Experimental arm
Days -13 or -7 to day 0 total 7 or 14 days - oral sunitinib daily duration and dose as determined from the lead-in phase I study Cycle 1 day 1 - Cycle 1 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 2 day 1 - Cycle 2 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 3 day 1 - Cycle 3 AC 60600mgm2 days 15-21 - oral sunitinib daily Cycle 4 day 1 - Cycle 4 AC 60600mgm2
DCE-MRI scan will be performed serially to determine tumor response and change in tumor vascular parameters for each enrolled subject
Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1 and on days 1 and 15 of each subsequent cycle In addition patients in Arm B will be evaluated weekly during the first two weeks of sunitinib administration prior to cycle 1 AC
Detailed Description:
Special tests Blood sampling
Germline DNA at baseline for pharmacogenetics analysis
Pharmacokinetic sampling for doxorubicin and cyclophosphamide on day 1 cycle 1 of AC administration
Pharmacokinetic sampling for sunitinib at baseline and weekly during the first course of sunitinib for subjects in Arm B before the sunitinib dose on that day
Serial plasma samples for proteomics analysis and for analysis of soluble angiogenic factors
Serial whole blood for gene expression analysis
Serial blood samples for circulating tumor and circulating endothelial cells
DNA will be extracted from collected snap-frozen andor paraffin-embedded tumor tissue sections pre- and post-treatment and plasma pre- and post-treatment taken for plasma biomarker analysis Primary tumor and circulating tumor DNA will be genotyped for cancer genes of interest that may influence cancer prognosis andor treatment response
Tumor core biopsy Arm A Performed at baseline approximately 3 weekly after cycle 1 AC but before cycle 2 AC and upon completion of 4 cycles of AC for a total of 3 tumor core biopsies Arm B Performed at baseline after completing the first course of sunitinib and before cycle 1 AC approximately 3 weekly after cycle 1 AC but before cycle 2 AC and upon completion of 4 cycles of AC for a total of 4 tumor core biopsies
The final biopsy may be obtained at surgery if the patient is scheduled for lumpectomy or mastectomy The tumor cores will be stored in liquid nitrogen for subsequent DNA RNA and protein extraction for biomarker studies including gene expression and proteomics analyses Three to four samples will be obtained at each time point and one tumor core at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers
Note Tumor biopsies imaging and blood collection that are to be conducted after completing the first course of sunitinib may be carried out as early as 2 days before the last dose of sunitinib in the first course for logistics reasons
Germline DNA at baseline for pharmacogenetics analysis
Pharmacokinetic sampling for doxorubicin and cyclophosphamide on day 1 cycle 1 of AC administration
Pharmacokinetic sampling for sunitinib at baseline and weekly during the first course of sunitinib for subjects in Arm B before the sunitinib dose on that day
Serial plasma samples for proteomics analysis and for analysis of soluble angiogenic factors
Serial whole blood for gene expression analysis
Serial blood samples for circulating tumor and circulating endothelial cells
DNA will be extracted from collected snap-frozen andor paraffin-embedded tumor tissue sections pre- and post-treatment and plasma pre- and post-treatment taken for plasma biomarker analysis Primary tumor and circulating tumor DNA will be genotyped for cancer genes of interest that may influence cancer prognosis andor treatment response
Tumor core biopsy Arm A Performed at baseline approximately 3 weekly after cycle 1 AC but before cycle 2 AC and upon completion of 4 cycles of AC for a total of 3 tumor core biopsies Arm B Performed at baseline after completing the first course of sunitinib and before cycle 1 AC approximately 3 weekly after cycle 1 AC but before cycle 2 AC and upon completion of 4 cycles of AC for a total of 4 tumor core biopsies
The final biopsy may be obtained at surgery if the patient is scheduled for lumpectomy or mastectomy The tumor cores will be stored in liquid nitrogen for subsequent DNA RNA and protein extraction for biomarker studies including gene expression and proteomics analyses Three to four samples will be obtained at each time point and one tumor core at each time point will be stored in formalin and paraffin-embedded for immunohistochemistry analysis of biomarkers
Note Tumor biopsies imaging and blood collection that are to be conducted after completing the first course of sunitinib may be carried out as early as 2 days before the last dose of sunitinib in the first course for logistics reasons
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