Ignite Creation Date:
2025-12-24 @ 12:41 PM
Ignite Modification Date:
2025-12-29 @ 7:32 AM
Study NCT ID:
NCT03803761
Status:
WITHDRAWN
Last Update Posted:
2023-09-25
First Post:
2019-01-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of a New Drug Combination, Copanlisib and Fulvestrant, in Advanced Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 2 Study of Copanlisib (BAY 80-6946) in Combination With Fulvestrant in Patients With Metastatic Breast Cancer Progressing After Aromatase Inhibitor Plus CDK 4/6 Inhibitor
Status:
WITHDRAWN
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inadequate accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the side effects and how well copanlisib works when given together with fulvestrant in treating patients with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) breast cancer that has spread to other places in the body (advanced) and progressing after prior treatment. HER2 and ER are two types of proteins called receptors that can affect the growth of breast cancer cells. Additionally, investigators hope to learn from this study if tumor genetic information is important for predicting whether this type of breast cancer will respond to fulvestrant and copanlisib. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving copanlisib and fulvestrant may work better in treating patients with ER+ and HER2- breast cancer compared to fulvestrant alone.
Detailed Description:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
I. Estimate progression-free survival (PFS) in patients treated with copanlisib and fulvestrant stratifying by actionable PIK3CA mutation, actionable PIK3CA or PTEN mutation, or wild type PIK3CA and PTEN.
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.
EXPLORATORY OBJECTIVES:
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 PFS in patients with baseline ctDNA PIK3CA actionable mutations versus (vs.) those with wild type PK3CA.
VI. To evaluate genomic and gene expression changes in tumor cells and in associated tumor microenvironment before and after administration of copanlisib in combination with fulvestrant and at the time of progression.
VII. Evaluate circulating markers of metabolism before and after PI3K inhibitor therapy which may predict treatment response and resistance mechanisms.
OUTLINE:
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.
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.
SECONDARY OBJECTIVES:
I. Estimate progression-free survival (PFS) in patients treated with copanlisib and fulvestrant stratifying by actionable PIK3CA mutation, actionable PIK3CA or PTEN mutation, or wild type PIK3CA and PTEN.
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.
EXPLORATORY OBJECTIVES:
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 PFS in patients with baseline ctDNA PIK3CA actionable mutations versus (vs.) those with wild type PK3CA.
VI. To evaluate genomic and gene expression changes in tumor cells and in associated tumor microenvironment before and after administration of copanlisib in combination with fulvestrant and at the time of progression.
VII. Evaluate circulating markers of metabolism before and after PI3K inhibitor therapy which may predict treatment response and resistance mechanisms.
OUTLINE:
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: