A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer
|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
|Drug: Anastrozole Drug: AZD0530|
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.
|Drug: Anastrozole Drug: AZD0530|
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.
|Drug: Anastrozole Drug: Placebo|
- 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
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|