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Anatomic Stage III Breast Cancer AJCC v8Phase 1/2NCT04345913

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

A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 43 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
43 sitesUnited States
Study dates
1 Mar 2021to 31 May 2027
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients must have metastatic or unresectable carcinoma of the breast that is estrogen receptor (ER) negative (less than 10%), progesterone receptor (PR) negative (less than 10%), and HER2 negative/unamplified
  • Patients must have had prior treatment with an anthracycline and taxane in the neoadjuvant, adjuvant, or metastatic setting, unless contraindicated or deemed to be suboptimal therapy per the treating physician
  • Patients must have progressed on at least one and not more than five prior chemotherapy regimens, including in the neoadjuvant, adjuvant, and metastatic settings. Prior chemotherapy in the neoadjuvant and/or adjuvant setting counts as one prior line. Prior endocrine therapy, anti-HER2 directed therapies, PARP inhibitors, immunotherapy alone, or other targeted therapy will not count as a prior therapy line, as long as the patient meets the eligibility criteria prior to enrollment. Immunotherapy combined with chemotherapy will be considered one line
  • All patients must agree to provide archival tumor material (most recent archival tumor tissue immediately prior to enrollment is strongly preferred) for research and must agree to undergo research tumor biopsy before treatment if presence of easily accessible lesions (judged by the treating physician). For patients with bone only disease, or patients without easily accessible lesions for the baseline research biopsy, availability of archival tumor material (2 x 4-5 micron section unstained slides, plus 15-20 x 10 micron section unstained slides or a tumor rich block) from previous breast cancer diagnosis or treatment is required for PTEN and PIK3CA analysis
  • Age >= 18 years. Because no dosing or adverse event data are currently available on the use of copanlisib in combination with eribulin in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
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  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.0 g/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (=< 3 x institutional ULN for patients with Gilbert syndrome)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
  • Lipase =< 1.5 x ULN
  • Creatinine < 1.5 mg/dL AND glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2
  • International normalized ratio (INR) =< 1.5 x ULN
  • Partial thromboplastin time (PTT) =< 1.5 x ULN
  • Patients with history of known type I or type II diabetes must have a fasting glucose level of < 120 mg/dL on at least 2 separate occasions or glycosylated hemoglobin measurement (HbA1c) < 8.5% at screening within 14 days prior to registration
  • Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that their medication dose and INR/PTT is stable
  • Prophylactic antiemetics may be administered according to standard practice. The routine use of standard antiemetics, including 5-HT3 blockers, such as granisetron, ondansetron, or an equivalent agent, is allowed as needed, as long as corrected QT (QTc) interval on baseline electrocardiogram (ECG) < 480 msec. The use of corticosteroids as antiemetics prior to copanlisib administration will not be allowed
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial provided they are on a stable regimen of anti-retroviral therapy (ART) with no medications otherwise prohibited by this protocol (e.g. drug-drug interactions)
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. For patients with history of treated brain metastases, brain scans will be performed within 6 weeks of study enrollment. During study enrollment in the phase 2 portion of the study, brain MRI will be performed every 12 weeks or sooner if clinically-indicated in all patients with history of known brain metastases
  • For phase 1 portion of the study only: patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. This is not allowed for phase 2 portion of the study
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Patients with history of known congestive heart failure (left ventricular ejection fraction [LVEF] < 50%) must have documented LVEF >= 50% within 12 months of study enrollment
  • Known mutation status for PIK3CA and PTEN from archival tumor tissue analysis
  • The effects of copanlisib on the developing human fetus are unknown. For this reason and because maternal toxicity, developmental toxicity and teratogenic effects have been observed in nonclinical studies and PI3K inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 1 month after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3.5 months after completion of study treatment
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 3 weeks of treatment start (cycle 1 day 1 [C1D1])
  • Patients who have had prior treatment with nitrosoureas or mitomycin C
  • Patients who have had prior treatment with eribulin
  • Patients who have had prior treatment with PI3K/mTOR/AKT pathway inhibitor
  • Clinically significant ECG abnormality, including prolonged corrected QT (QTc) interval > 480 msec or history of risk factors for Torsades de Pointes (TdP) (i.e. congestive heart failure, hypokalemia, hypomagnesemia, bradyarrhythmias, family history of long QT syndrome)
  • Patients with pre-existing neuropathy of grade 2 or higher
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  • Myeloid growth factors within 7 days prior to treatment start
  • Platelet transfusion within 7 days prior to treatment start
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents
  • Immunosuppressive therapy is not allowed while on study
  • Known tumor AKT mutation from archival tumor tissue analysis
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, or other agents used in study
  • Copanlisib is primarily metabolized by CYP3A4. Therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted from 14 days prior to enrollment until the end of the study. Other medications that are prohibited while on copanlisib treatment:
  • Herbal medications/preparations (except for vitamins)
  • Anti-arrhythmic therapy other than beta blockers or digoxin
  • Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study. Previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days prior to the CT/MRI screening. If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening. Patients may be using topical or inhaled corticosteroids. Short-term (up to 7 days) systemic corticosteroids above 15 mg prednisolone or equivalent will be allowed for the management of acute conditions (e.g., treatment non-infectious pneumonitis). The use of corticosteroids as antiemetics prior to copanlisib administration will not be allowed
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with non-healing wound, ulcer, or bone fracture. Patients with compression or pathologic fractures that are stable in the opinion of the investigator may be enrolled, as long as the bone fracture is not felt to pose a high likelihood of treatment delay or difficulties in treatment adherence as per the judgement of the investigator
  • Patients with active, clinically serious infections > grade 2 (Common Terminology Criteria for Adverse Events Version 5.0 [CTCAEv5.0]) (viral, bacterial or fungal infection)
  • History of known Pneumocystis jiroveci pneumonia (PJP) infection
  • Patients with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
  • Concurrent diagnosis of pheochromocytoma due to risk of hypertension with copanlisib
  • Uncontrolled hypertension (defined as blood pressure >= 150/90 mm/Hg) despite optimal medical management (per investigator's opinion)
  • Proteinuria as estimated by urine protein/creatinine ratio > 3.5 g/g on random urine sample or grade >= 3 as assessed by 24-hour urine protein collection
  • Patients with history of or current uncontrolled autoimmune disease. Patients who have adrenal or pituitary insufficiency who are stable on replacement therapy (i.e. thyroxine or physiologic corticosteroid replacement therapy that meets concomitant medication restrictions) are allowed. Limited exceptions may be made to this after discussion with the study principal investigator (PI)
  • Patients with congenital QT prolongation
  • The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
  • Pregnant women are excluded from this study because copanlisib is a PI3K inhibitor agent and eribulin is an anti-tubulin agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with copanlisib and eribulin, breastfeeding should be discontinued if the mother is treated with copanlisib and/or eribulin. These potential risks may also apply to other agents used in this study

Trial locations and contacts

43 sites in 1 country.

43 sites in 1 country

United States43 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • UM Sylvester Comprehensive Cancer Center at Aventura

    Aventura, Florida, 33180

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Smilow Cancer Hospital Care Center at Glastonbury

    Glastonbury, Connecticut, 06033

  • Smilow Cancer Hospital Care Center at Greenwich

    Greenwich, Connecticut, 06830

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • UM Sylvester Comprehensive Cancer Center at Plantation

    Plantation, Florida, 33324

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Memorial Hospital East

    Shiloh, Illinois, 62269

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Smilow Cancer Hospital Care Center at Long Ridge

    Stamford, Connecticut, 06902

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wake Forest Baptist Health - Wilkes Medical Center

    Wilkesboro, North Carolina, 28659

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

  1. 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).

  1. 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.

Being tested
Biopsy Procedure, Biospecimen Collection, Computed Tomography, Copanlisib Hydrochloride, Eribulin Mesylate
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Copanlisib HydrochlorideDrug

    Also called 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride

    Given IV

  • Eribulin MesylateDrug

    Also called B1939 Mesylate, E7389, ER-086526 Mesylate, Halaven

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

Study groups in NCT04345913
Study groupRoleWhat they receive
Group I (Phase II, eribulin)Active comparatorGroup I (Phase II): 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. Additionally, patients undergo a CT scan and/or 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Eribulin Mesylate; Procedure: Magnetic Resonance Imaging
Group II (Phase II, DL1, eribulin, copanlisib)ExperimentalGroup II (Phase II, 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 CT scan and/or 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Drug: Eribulin Mesylate; Procedure: Magnetic Resonance Imaging
Phase I, DL1 (eribulin, copanlisib)ExperimentalPhase I, 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 CT scan and/or 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Drug: Eribulin Mesylate; Procedure: Magnetic Resonance Imaging
Phase I, DL2 (eribulin, copanlisib)ExperimentalPhase 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. Additionally, patients undergo a CT scan and/or 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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Drug: Eribulin Mesylate; Procedure: Magnetic Resonance Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose of Eribulin (MTD) (Phase I)

    MTD is defined as the highest dose level of eribulin at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

    Measured: Up to 28 days

  2. Recommended Phase 2 Dose of Eribulin (RP2D) (Phase I)

    RP2D is the maximum tolerated dose of eribulin at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

    Measured: Up to 28 days

  3. Maximum Tolerated Dose of Copanlisib (MTD) (Phase I)

    MTD is defined as the highest dose level of copanlisib at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

    Measured: Up to 28 days

  4. Recommended Phase 2 Dose of Copanlisib (RP2D) (Phase I)

    RP2D is the maximum tolerated dose of copanlisib at which at most 1 of 6 patients experience a dose limiting toxicity during the observation window.

    Measured: Up to 28 days

  5. Progression Free Survival (PFS) (Phase II)

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who have not experienced progression or death will be censored at last follow up. PFS will be estimated using the Kaplan-Meier product limit estimator.

    Measured: From date of treatment start to date of progression or death, assessed up to 36 months

Secondary outcomes (5)

  1. Objective Response Rate (ORR) (Phase I)

    ORR is defined as the proportion of patients with complete response, partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.

    Measured: Up to 36 months

  2. Clinical Benefit Rate (CBR) (Phase I)

    CBR defined as the proportion of patients with clinical benefit (complete response, partial response and stable disease lasting > 24 weeks) per RECIST v1.1 in the overall population, and by PTEN/PIK3CA mutation status based on archival tumor tissue next generation sequencing. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither 30% shrinkage of longest diameter of target lesions to qualify for PR nor 20% increase in longest diameter of target lesion to qualify for PD, for a period of time greater than 24 weeks.

    Measured: Up to 36 months

  3. ORR (Phase II)

    ORR is defined as the proportion of patients with complete response, partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR) = CR + PR.

    Measured: Up to 36 months

  4. CBR (Phase II)

    CBR is defined as the proportion of patients with clinical benefit (complete response, partial response, and stable disease lasting ≥ 24 weeks) per RECIST v1.1 in each arm. Per RECIST 1.1, target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither 30% shrinkage of longest diameter of target lesions to qualify for PR nor 20% increase in longest diameter of target lesion to qualify for PD, for a period of time greater than 24 weeks.

    Measured: Up to 36 months

  5. PFS (Phase I)

    PFS is defined from date of treatment start to date of progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Patients who have not experienced progression or death will be censored at last follow up. PFS will be estimated using the Kaplan-Meier product limit estimator.

    Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2020
  2. Study start1 Mar 2021
  3. Primary completion28 Mar 2024
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04345913
Sponsor's protocol ID
NCI-2020-02319
Other IDs
NCI-2020-02319, 202010089, 10382, 10382, UM1CA186689, UM1CA186704
Status last verified
May 2026
First submitted
14 Apr 2020
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by National Cancer Institute (NCI) at 43 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose of Eribulin (MTD) (Phase I) (time frame: Up to 28 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04345913.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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