Trials / Active Not Recruiting

Active Not RecruitingNCT04345913

Testing the Addition of Copanlisib to Eribulin in Metastatic Triple Negative Breast Cancer

A Phase I/II Trial Evaluating the Safety and Efficacy of Eribulin in Combination With Copanlisib in Patients With Metastatic Triple Negative Breast Cancer

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 24 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of copanlisib and how well it works when given together with eribulin in treating patients with triple negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving copanlisib and eribulin together may work better in treating advanced stage triple negative breast cancer compared to eribulin alone.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety, toxicity profile, dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of copanlisib hydrochloride (copanlisib) in combination with eribulin mesylate (eribulin) in metastatic triple negative breast cancer (TNBC). (Phase I) II. To compare progression free survival (PFS) between eribulin and eribulin plus copanlisib arms in patients with metastatic TNBC treated with prior taxane and anthracycline. (Phase II) SECONDARY OBJECTIVES: I. To determine the objective response rate (ORR) and clinical benefit rate (CBR) of the combination. (Phase I) II. To observe and record anti-tumor activity. (Phase I) III. To compare the ORR, CBR (complete response \[CR\]+partial response \[PR\]+stable disease \[SD\] \>= 24 weeks) and safety of eribulin and eribulin plus copanlisib arms. (Phase II) EXPLORATORY OBJECTIVES: I. To compare PTEN (immunohistochemistry) IHC results between paired baseline tumor biopsy versus at time of disease progression. II. Assess baseline (pre-treatment) tumor tissue mutation or gene expression profiles to correlate treatment response. III. Assess intrinsic and adaptive resistance mechanisms by analyzing pre and post treatment biopsies for gene expression and proteomic changes. IV. Determine circulating tumor DNA (ctDNA) mutation profiles at baseline and changes in mutation profile and variant allele frequencies (VAFs) on cycle 2 day 1 (C2D1) and at disease progression compared to baseline to correlate with treatment response. V. Assess circulating biomarkers predictive of treatment response. VI. Assess plasma and serum proteomics and metabolomics predictive of treatment response. VII. To compare the ORR, CBR, PFS of eribulin and eribulin plus copanlisib arms in patients with tumors harboring mutations in PIK3CA/ PTEN or with loss of PTEN expression by IHC on baseline tumor biopsy. VIII. To compare the ORR, CBR, PFS of eribulin and eribulin plus copanlisib arms in patients with tumors lacking PIK3CA/ PTEN pathway alterations. IX. To compare the ORR, CBR, PFS of eribulin and eribulin plus copanlisib arms in patients with tumors harboring loss of PTEN expression by IHC in pre-treatment metastatic site (in patients with available tissue from metastatic site). X. To compare PTEN IHC results between paired archival primary tumor versus (vs.) baseline tumor biopsies. XI. To assess targeted inhibition by copanlisib and eribulin by measuring treatment induced changes in phosphorylated (phospho)-AKT (T308), phospho-AKT (S473), phospho-histone H3, and inhibition of apoptosis (cleaved caspase 3) between post-treatment tumor (C2D1-2) versus baseline. XII. To compare the ORR, CBR, PFS of eribulin and eribulin plus copanlisib arms in patients with tumors harboring mutations in PIK3CA/PTEN by circulating tumor deoxyribonucleic acid (ctDNA) at baseline, and potential changes over time. OUTLINE: This is a phase I dose-escalation study of copanlisib and eribulin followed by a phase II study. Patients are randomized to 1 of 2 groups. Phase I, DL1: Patients receive copanlisib (45 mg) intravenously (IV) over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Phase I, DL2: Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Group I (Phase II, eribulin): Patients receive eribulin (1.4 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Group II (Phase II, eribulin + copanlisib, DL1): Patients receive copanlisib (45 mg) IV over 1 hour and eribulin (1.1 mg/m\^2) IV over 2 to 5 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) at screening, cycle 3 day 1, and every 9 weeks thereafter. Patients also undergo a biopsy at baseline, cycle 2 day 1, and at time of disease progression as well as blood sample collection at baseline, cycle 2 day 1, every 9 weeks and at time of disease progression. After completion of study treatment, patients are followed every 3 months for up to 36 months.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Copanlisib Hydrochloride	Given IV
DRUG	Eribulin Mesylate	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI

Timeline

Start date: 2021-03-01
Primary completion: 2024-03-28
Completion: 2026-05-07
First posted: 2020-04-15
Last updated: 2026-04-13
Results posted: 2025-07-28

Locations

43 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04345913. Inclusion in this directory is not an endorsement.