Testing the Addition of Copanlisib to Eribulin for the Treatment of Advanced-Stage 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

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) IV. 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 immunohistochemistry (IHC) on baseline tumor biopsy. (Phase II) V. To compare the ORR, CBR, PFS of eribulin and eribulin plus copanlisib arms in patients with tumors lacking PIK3CA/ PTEN pathway alterations. (Phase II) VI. 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). (Phase II) VII. To compare PTEN IHC results between paired archival primary tumor versus (vs.) baseline tumor biopsies. (Phase II) VIII. 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. (Phase II) IX. 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-derived deoxyribonucleic acid (ctDNA) at baseline, and potential changes over time. (Phase II)EXPLORATORY OBJECTIVES:I. To compare PTEN 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.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.GROUP I: Patients receive eribulin intravenously (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: Patients receive copanlisib IV over 1 hour and eribulin 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.Patients in both groups also 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 and 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..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 03. Jan. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Breast Neoplasms Carcinoma Phase: Phase 1, Phase 2 Recruitment Status: Active, not recruiting Study Type: Interventional Triple Negative Breast Neoplasms

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: April 15, 2020, Last downloaded: ClinicalTrials.gov processed this data on January 10, 2024, Last updated: January 10, 2024

Study ID:	NCT04345913 NCI-2020-02319 202010089 10382 UM1CA186689 UM1CA186704
Veröffentlichungen zur Studie:

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PPN (Katalog-ID):	CTG003359212