A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01216176|
Recruitment Status : Completed
First Posted : October 7, 2010
Last Update Posted : February 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Anastrozole Drug: AZD0530 Drug: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase I Pharmacokinetic and Randomized Phase II Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer|
|Actual Study Start Date :||October 21, 2008|
|Actual Primary Completion Date :||February 7, 2018|
|Actual Study Completion Date :||February 7, 2018|
Experimental: Phase 1 - Cohort A
Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 175 mg orally once daily, or as specified per protocol, until disease progression for treatment of metastatic breast cancer
Active Comparator: Phase 2 - Cohort B [Anastrozole + AZD0530]
Dual treatment with 1 mg anastrozole orally once daily together with AZD0530 175 mg orally once daily, or as specified per protocol, until disease progression or 4-6 months of treatment completed.
Placebo Comparator: Phase 2 - Cohort B [Anastrozole + Placebo]
Dual treatment with 1 mg anastrozole orally once daily together with Placebo orally once daily, or as specified per protocol, until disease progression or4-6 months of treatment completed.
- Phase I Cohort A: To determine if a well tolerated dose of AZD0530 can be used in combination with anastrozole for postmenopausal women with ER+/PR+ metastatic breast cancer [ Time Frame: Cycle 1: Days 1 - 28 ]
- Phase II - Cohort B: Compare treatment groups (AZD0530 + Anastrozole versus Anastrozole with placebo) with respect to clinical response [ Time Frame: At the end of each 28 day cycle, for a total of 4- 6 cycles ]Clinical response is defined as percentage change/reduction in tumor size calculated from bi-dimensional clinical tumor measurement at diagnosis and on completion of neoadjuvant treatment.
- Phase I - Cohort A: To test the effects of giving AZD0530 and Anastrozole together on pharmacokinetics of both drugs [ Time Frame: Cycle 1: 0 hrs, 6 hrs, 12 hrs, 24hrs, 48 hrs, 72 hrs, 7 days, 14 days, 21 days after first dose of AZD0530 ]Blood draws at protocol-specified timepoints to determine pharmacokinetics of AZD0530 and Anastrozole.
- Phase II - Cohort B: Evaluation of pathologic complete response (pCR) [ Time Frame: At the end of neoadjuvant therapy and after definitive surgery ]Evaluation of tumor specimen in patients undergoing mastectomy or breast-conserving procedure to determine response (pCR)
- Phase II - Cohort B: Clinical Benefit (complete (CR), or partial (PR) responses or stable disease (SD)) [ Time Frame: At the end of neoadjuvant therapy ]Based on physician measurement of tumor size and by MRI measurements of tumor volume at diagnosis and prior to surgery.
- Phase II - Cohort B: Qualitative and Quantitative Toxicities [ Time Frame: Baseline, 4-6 treatment cycles and up to 4-6 weeks after surgery or after therapy/withdrawal or until resolution of any toxicity ]Patients who have tumor removal breast surgery after neoadjuvant therapy will be assessed up to 2 months after surgery. In the event the tumor is not-operable, toxicity will evaluated by patient interview and examination for the last time 4-6 weeks after discontinuing therapy or when toxicity is resolved.
- Phase II - Cohort B: To identify molecular/biologic correlates as indicators of treatment response [ Time Frame: At the end of neoadjuvant therapy and after definitive surgery ]Evaluation of biomarkers including Ki67 and p27, EGFR, Her2, Src, Akt and MAPK Levels, localization and phosphorylation as assayed by immunohistochemistry. Other biomarkers may be considered pending initial IHC results.
- Phase II cohort B: Evaluation of clinical response defined as percentage change/reduction in tumor size by comparison of serial MRI [ Time Frame: Baseline , 10 weeks from study start date and pre-operative ]MRI will be used to compare tumor size prior to drug therapy , at 10 weeks after start of treatment and prior to surgery after completion of study medication
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01216176
|United States, California|
|Palo Alto, California, United States, 94304|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|Principal Investigator:||Joyce Slingerland, MD||University of Miami|