PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer
A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67>10% compared to historical control.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Neoadjuvant PD 0332991, a Cyclin-Dependent Kinase (Cdk) 4/6 Inhibitor, in Combination With Anastrozole in Women With Clinical Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer|
- Complete cell cycle arrest in women without PIK3CA hotspot mutation [ Time Frame: 2 weeks (C1D15) ] [ Designated as safety issue: No ]Complete cell cycle arrest is defined as Ki67 < 2.7% following 2 weeks of neoadjuvant PD 0332991
- PEPI 0 score [ Time Frame: 30 days following the last day of study treatment. ] [ Designated as safety issue: No ]
- Clinical response and radiologic response [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Physical examination: Prior cycle 0 and at the end of each neoadjuvant treatment cycle cycles (that is, at the end of cycles 0-4) the longest axis and the perpendicular axis of the measurable lesion should be measured and recorded in metric notation by tape, ruler or caliper technique on the case report forms.
Radiographic evaluation of tumor size: Mammogram and ultrasound imaging will be performed prior to cycle 0 and at the end of cycle 4 combination therapy for bidimensional measurement of the tumor.
WHO criteria will be used to assess clinical response:
- Ki67 level post 2 weeks of PD 332991 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
Following the approach of Dowsett et al., the percent change in the Ki67 level from baseline will be determined on the log scale. A 95% t-confidence interval for the mean percent change in the Ki67 level from baseline will be constructed (if appropriate).
Logistic regression modeling will be used to examine which baseline patient and/or tumor characteristics are associated with the likelihood of a Ki67 being at or below 10%.
- concentration of PD 0332991 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Blood will be drawn for PKs on Cycle 1 Day 15. At each time point, blood will be drawn prior to drug administration and 90 minutes following drug administration. This will be done in the first 16 patients in the PIK3CA wild type cohort only.
- Complete cell cycle arrest rate at C1D1 and C1D15 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Compare rate of complete cell cycle (defined as Ki67 < 2.7%) arrest between C1D1 and C1D15
- Ki67 level of tumor specimens [ Time Frame: 5 months ] [ Designated as safety issue: No ]To assess Ki67 level on serially collected tumor specimens (baseline, C1D1, C1D15, and time of surgery)
- Pathologic complete response (pCR) rate [ Time Frame: 5 months ] [ Designated as safety issue: No ]
- concentration of anastrozole [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Blood will be drawn for PKs prior to initiation of PD 0332991 but after patients have taken anastrozole alone or in combination with goserelin for at least 2 weeks (this could be done on Cycle 1 Day 1) and again on Cycle 1 Day 15. At each time point, blood will be drawn prior to drug administration and 90 minutes following drug administration. This will be done in the first 16 patients in the PIK3CA wild type cohort only.
- Safety of PD 0332991 in combination in anastrozole [ Time Frame: 15 weeks ] [ Designated as safety issue: Yes ]The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
- Complete cell cycle arrest in women with PIK3CA hotspot mutation [ Time Frame: 2 weeks (C1D15) ] [ Designated as safety issue: No ]Complete cell cycle arrest is defined as Ki67 < 2.7% following 2 weeks of neoadjuvant PD 0332991
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: PD0332991+ Anastrozole
PD0332991 125 mg orally Days 1-21 of each 28 day cycle.
Anastrozole 1 mg orally on Days 1-28 of each cycle.
If premenopausal Goserelin 3.6 mg SC on Day 1.
Treatment with PD 0332991 combined with anastrozole (and goserelin if premenopausal) is for a maximum of 4 28-day cycles prior to surgery.
Anastrozole is to be continued until the day of surgery. The last dose is on the day before surgery.
Other Name: Arimidex®Drug: Goserelin
Please refer to this study by its ClinicalTrials.gov identifier: NCT01723774
|Contact: Cynthia Ma, M.D., Ph.D.||email@example.com|
|United States, Alabama|
|University of Alabama||Recruiting|
|Birmingham, Alabama, United States, 35233|
|Contact: Andres Forero, M.D. 205-934-7167 firstname.lastname@example.org|
|United States, Arizona|
|Mayo Clinic - Scottsdale||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Donald W Northfelt, M.D. 480-301-8000 email@example.com|
|Principal Investigator: Donald W Northfelt, M.D.|
|United States, Minnesota|
|Mayo Clinic - Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Matthew Goetz, M.D. 507-284-2511 firstname.lastname@example.org|
|Principal Investigator: Matthew Goetz, M.D.|
|Sub-Investigator: Tina Hieken, M.D.|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|St. Louis, Missouri, United States, 63122|
|Contact: Cynthia Ma, M.D., PH.D. 314-362-9383 email@example.com|
|Principal Investigator: Cynthia Ma, M.D., Ph.D.|
|Sub-Investigator: Julie Margenthaler, M.D.|
|Sub-Investigator: Souzan Sanati, M.D.|
|Sub-Investigator: Hussam Al-Kateb, M.Sc, Ph.D.|
|United States, Texas|
|Baylor College of Medicine||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Contact: Matthew Ellis, M.B. firstname.lastname@example.org|
|Principal Investigator:||Cynthia Ma, M.D., Ph.D.||Washington University School of Medicine|