Study of a New Drug Combination, Copanlisib and Fulvestrant, in Postmenopausal Women With Advanced Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03803761|
Recruitment Status : Not yet recruiting
First Posted : January 15, 2019
Last Update Posted : February 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Breast Carcinoma Metastatic in the Brain Estrogen Receptor Positive HER2/Neu Negative Metastatic Breast Carcinoma Postmenopausal Prognostic Stage IV Breast Cancer AJCC v8||Drug: Copanlisib Drug: Fulvestrant||Phase 1 Phase 2|
I. Establish safety of the combination of copanlisib and fulvestrant (FC). II. Evaluate the response rate (RR) of the combination of copanlisib and fulvestrant in patients with estrogen-receptor positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer that has previously progressed on aromatase inhibitor (AI)/cyclin dependent kinase (CDK) 4/6 inhibitor therapy.
I. Estimate progression-free survival (PFS) in patients treated with copanlisib and fulvestrant.
II. Estimate the RR in subjects with PTEN loss by immunohistochemistry (IHC) analysis performed retrospectively.
III. Evaluate toxicity in patients treated with FC in Phase II.
I. Evaluate copanlisib pharmacokinetics (PK) when given in combination with fulvestrant.
II. Explore association between intrinsic subtype and response to FC therapy. III. Assess baseline levels and treatment-induced proteomic changes and correlate with response to FC.
IV. Evaluate circulating tumor deoxyribonucleic acid (DNA) (ctDNA) mutations at baseline and over time for response predictors at baseline, clonal evolution associated with treatment, and resistance mechanisms at disease progression.
V. Evaluate circulating markers of metabolism before and after PI3K inhibitor therapy which may predict treatment response and resistance mechanisms.
Patients receive copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15 and fulvestrant intramuscularly (IM) over 1-2 minutes on days 1 and 15 of cycle 1 and on day 1 beginning cycle 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Copanlisib (BAY 80-6946) in Combination With Fulvestrant in Women With Metastatic Breast Cancer Progressing After Aromatase Inhibitor Plus CDK 4/6 Inhibitor|
|Estimated Study Start Date :||February 12, 2019|
|Estimated Primary Completion Date :||March 31, 2020|
|Estimated Study Completion Date :||March 31, 2020|
Experimental: Treatment (copanlisib, fulvestrant)
Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 and fulvestrant IM over 1-2 minutes on days 1 and 15 of cycle 1 and on day 1 beginning cycle 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Dose limiting toxicity (DLT) [ Time Frame: Up to 30 days post treatment ]Toxicities will be tabulated based on type and grade.
- Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, assessed up to 30 days post treatment ]PFS will be estimated using the Kaplan Meier method, with median and 95% confidence interval (CI) reported.
- Response rate [ Time Frame: Up to 30 days post treatment ]Response rate will be reported for subjects with PTEN loss by immunohistochemistry (IHC) analysis performed retrospectively. This will be done across cohorts.
- Incidence of adverse events [ Time Frame: Up to 30 days post treatment ]Toxicities will be tabulated based on type and grade. Any toxicity seen in more than 10% of patients will be reported, and all grade 3-4 toxicities will be reported.
- Pharmacokinetics (PK) and pharmacodynamic data (RPPA) [ Time Frame: Up to 30 days post treatment ]Descriptive statistics will be provided.
- Biomarkers analysis [ Time Frame: Up to 30 days post treatment ]Prognostic effect of biomarker for PFS will be examined by the Kaplan Meier (KM) method or/and Cox proportional hazard model and for objective response rate (ORR) using logistic regression model. Predictive effect of biomarker will be explored by examining the interaction effect of biomarker and arm in Cox or logistic regression model. For markers measured along multiple time points, generalized linear mixed effects model will be used to model longitudinal trajectories along time with the inference focus on the arm factor, without and with adjustment for other covariates. Two sample t-test or Wilcoxon rank sum test will be applied to compare time-matched biomarkers between the two arms or two patient subsets. Paired sample t-test or Wilcoxon signed rank test will be applied to compare subject-specific biomarkers between two time points. Multiple comparisons will be adjusted to control false discovery rate. Proposed subset analyses will be applicable to biomarkers.
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): NCT03803761
|Principal Investigator:||Elizabeth C Dees||Duke University - Duke Cancer Institute LAO|