Dinaciclib and Epirubicin Hydrochloride in Treating Patients With Metastatic Triple-Negative Breast Cancer
Estrogen Receptor Negative
Male Breast Carcinoma
Progesterone Receptor Negative
Recurrent Breast Carcinoma
Stage IV Breast Cancer
Triple-Negative Breast Carcinoma
Drug: Epirubicin Hydrochloride
Other: Laboratory Biomarker Analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study With Dose Expansion of Dinaciclib (SCH 727965) in Combination With Epirubicin in Patients With Metastatic Triple Negative Breast Cancer|
- MTD of dinaciclib given in combination with epirubicin hydrochloride, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 [ Time Frame: 21 days ]The number (%) of DLTs will tabulate by dose level of dinaciclib.
- Changes in proliferation as measured by Ki67 and apoptosis as measured by TUNEL [ Time Frame: From baseline to 2 weeks ]For the patients with pre- and post- treatment biopsies, summary statistics used to describe change in apoptotic index pre- to post-treatment, and boxplots to illustrate distribution pre- and post-treatment, as well as distribution of change. Mean change estimated with 95% confidence interval. MCL-1, LMW-E, and Ki67 similarly analyzed. Analyses also performed stratified by tumor grade. Correlation between changes in MCL-1 and LMW-E pre- to post-treatment estimated with 95% confidence interval. Number of tumors in 4 categories (negative, low, medium, high) tabulated by % of TUNEL+ tumor cells.
- Clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]), assessed using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: At 6 months ]The overall clinical benefit rate for patients treated at the MTD will be estimated with a 90% credible interval.
- Predictive value of MCL-1, LMW-E, and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy [ Time Frame: Up to 30 days after completion of study treatment ]A logistic regression model will be used to assess whether the expression level of LMW-E can predict clinical benefit, adjusted for dose level and other potential prognostic factors: visceral organ involvement (present vs. absent), number of prior therapies for metastatic breast cancer (0-2 or > 2), age (< 60 vs. > 60) and ECOG performance status (0-1 vs. 2).
|Actual Study Start Date:||August 21, 2012|
|Primary Completion Date:||September 16, 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dinaciclib and epirubicin hydrochloride)
Patients receive dinaciclib IV over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: Epirubicin Hydrochloride
Other Names:Other: Laboratory Biomarker Analysis
I. To determine the maximum tolerated dose (MTD) of dinaciclib given in combination with epirubicin in patients with metastatic triple negative breast cancer.
I. To determine the predictive value of myeloid cell leukemia sequence 1 protein (MCL-1), low molecular weight cyclin E (LMW-E), and tumor grade as predictors of biologic response (i.e. induction of apoptosis) in tumors treated with therapy.
II. To evaluate the efficacy of combination therapy. III. To determine the effects of therapy on proliferation as measured by proliferation-related Ki-67 antigen (Ki67) and apoptosis as measured by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay (TUNEL).
OUTLINE: This is a dose-escalation study of dinaciclib.
Patients receive dinaciclib intravenously (IV) over 2 hours on day 1 and epirubicin hydrochloride IV over 30 minutes on day 2. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01624441
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stacy Moulder||M.D. Anderson Cancer Center|