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
5 other identifiers
interventional
24
1 country
43
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2021
Longer than P75 for phase_1
43 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 14, 2020
CompletedFirst Posted
Study publicly available on registry
April 15, 2020
CompletedStudy Start
First participant enrolled
March 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2024
CompletedResults Posted
Study results publicly available
July 28, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 7, 2026
CompletedApril 13, 2026
November 1, 2025
3.1 years
April 14, 2020
June 25, 2025
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
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.
Up to 28 days
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.
Up to 28 days
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.
Up to 28 days
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.
Up to 28 days
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.
From date of treatment start to date of progression or death, assessed up to 36 months
Secondary Outcomes (5)
Objective Response Rate (ORR) (Phase I)
Up to 36 months
Clinical Benefit Rate (CBR) (Phase I)
Up to 36 months
ORR (Phase II)
Up to 36 months
CBR (Phase II)
Up to 36 months
PFS (Phase I)
From start of treatment to time of progression or death, whichever occurs first, assessed up to 36 months
Other Outcomes (8)
Tumor Tissue Mutation or Gene Expression Profiles
Up to 36 months
Intrinsic and Adaptive Resistance Mechanisms
Baseline up to 36 months
ctDNA Mutation Profiles and Changes in Mutation Profile and Variant Allele Frequencies (VAFs)
Baseline, cycle 2 day 1 (C2D2), and at disease progression
- +5 more other outcomes
Study Arms (4)
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.
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.
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.
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.
Interventions
Given IV
Undergo blood sample collection
Undergo CT scan
Given IV
Undergo MRI
Undergo biopsy
Eligibility Criteria
You may qualify if:
- 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%)
- 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
- +14 more criteria
You may not qualify if:
- 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
- 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)
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (43)
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418, United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut, 06824, United States
Smilow Cancer Hospital Care Center at Glastonbury
Glastonbury, Connecticut, 06033, United States
Smilow Cancer Hospital Care Center at Greenwich
Greenwich, Connecticut, 06830, United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437, United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut, 06105, United States
Yale University
New Haven, Connecticut, 06520, United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473, United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut, 06902, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Wake Forest Baptist Health - Wilkes Medical Center
Wilkesboro, North Carolina, 28659, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Nusayba Bagegni
- Organization
- Washington University in St. Louis School of Medicine
Study Officials
- PRINCIPAL INVESTIGATOR
Nusayba Bagegni
Washington University School of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 14, 2020
First Posted
April 15, 2020
Study Start
March 1, 2021
Primary Completion
March 28, 2024
Study Completion
May 7, 2026
Last Updated
April 13, 2026
Results First Posted
July 28, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
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.