Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2026-02-26 @ 12:36 AM
Study NCT ID:
NCT04108858
Status:
TERMINATED
Last Update Posted:
2025-10-01
First Post:
2019-09-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Maintenance Treatment (Trastuzumab and Pertuzumab) After Initial Chemotherapy in a Phase Ib/II Trial for Advanced HER2 Positive Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase Ib/II Trial of Copanlisib in Combination With Trastuzumab and Pertuzumab After Induction Treatment of HER2 Positive (HER2+) Metastatic Breast Cancer (MBC) With PIK3CA Mutation or PTEN Mutation
Status:
TERMINATED
Status Verified Date:
2025-09
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 Ib/II trial studies the side effects and best dose of copanlisib when given together with trastuzumab and pertuzumab and to see how well they work after induction treatment in treating patients with HER2 positive stage IV breast cancer with PIK3CA or PTEN mutation. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may kill tumor cells that are left after chemotherapy. The addition of copanlisib to the usual treatment (trastuzumab and pertuzumab) could shrink the cancer or stabilize it for longer duration as compared to the usual treatment alone.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the safety and recommended phase 2 dose (RP2D) of the combination of copanlisib, trastuzumab and pertuzumab in patients with metastatic epidermal growth factor receptor 2 (HER2)-positive breast cancer. (Phase Ib) II. To assess the benefit of adding copanlisib to trastuzumab and pertuzumab in HER2-positive metastatic breast cancer patients with PIK3CA mutations or PTEN mutation receiving maintenance therapy after induction treatment, as measured by progression free survival (PFS). (Phase II)
SECONDARY OBJECTIVES:
I. To assess the benefit of adding copanlisib to trastuzumab and pertuzumab in HER2-positive metastatic breast cancer patients with PIK3CA mutations or PTEN mutation receiving maintenance therapy after induction treatment, as measured by overall survival (OS). (Phase II) II. To evaluate the safety of copanlisib given at the RP2D in combination with trastuzumab and pertuzumab. (Phase II)
EXPLORATORY OBJECTIVES:
I. To correlate PFS and OS of the patients who receive the triplet combination with:
Ia. The number of induction cycles. Ib. Hormone receptor status (estrogen receptor \[ER\] and progesterone receptor \[PR\]).
Ic. PTEN loss by immunohistochemistry (IHC). Id. PIK3CA mutations or PTEN mutations. (Phase Ib)
II. To assess PTEN IHC, Ki-67 IHC and cleaved caspase-3 IHC and to perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to:
IIa. Identify potential predictive and prognostic biomarkers associated with treatment outcomes (PFS and OS) with the addition of copanlisib to dual HER2-targeted treatment.
IIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.
III. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
IV. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.
OUTLINE:
PHASE I: Patients receive copanlisib intravenously (IV) over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive copanlisib IV over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days and at 3 months.
I. To determine the safety and recommended phase 2 dose (RP2D) of the combination of copanlisib, trastuzumab and pertuzumab in patients with metastatic epidermal growth factor receptor 2 (HER2)-positive breast cancer. (Phase Ib) II. To assess the benefit of adding copanlisib to trastuzumab and pertuzumab in HER2-positive metastatic breast cancer patients with PIK3CA mutations or PTEN mutation receiving maintenance therapy after induction treatment, as measured by progression free survival (PFS). (Phase II)
SECONDARY OBJECTIVES:
I. To assess the benefit of adding copanlisib to trastuzumab and pertuzumab in HER2-positive metastatic breast cancer patients with PIK3CA mutations or PTEN mutation receiving maintenance therapy after induction treatment, as measured by overall survival (OS). (Phase II) II. To evaluate the safety of copanlisib given at the RP2D in combination with trastuzumab and pertuzumab. (Phase II)
EXPLORATORY OBJECTIVES:
I. To correlate PFS and OS of the patients who receive the triplet combination with:
Ia. The number of induction cycles. Ib. Hormone receptor status (estrogen receptor \[ER\] and progesterone receptor \[PR\]).
Ic. PTEN loss by immunohistochemistry (IHC). Id. PIK3CA mutations or PTEN mutations. (Phase Ib)
II. To assess PTEN IHC, Ki-67 IHC and cleaved caspase-3 IHC and to perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to:
IIa. Identify potential predictive and prognostic biomarkers associated with treatment outcomes (PFS and OS) with the addition of copanlisib to dual HER2-targeted treatment.
IIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.
III. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
IV. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Experimental Therapeutics Clinical Trials Network (ETCTN) Biorepository at Nationwide Children's Hospital.
OUTLINE:
PHASE I: Patients receive copanlisib intravenously (IV) over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive copanlisib IV over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days and at 3 months.
Study Oversight
Has Oversight DMC:
False
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?: