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

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Unresectable Triple-Negative Breast Carcinoma

In brief

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.

Key facts

Study ID

NCT04345913

Run by

National Cancer Institute (NCI)

People needed

24

Starts

2021-03-01

Expected to finish

2027-05-31

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• 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

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)
• 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)

Where it is running

• Emory University Hospital Midtown — Atlanta, Georgia, United States
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States
• Memorial Hospital East — Shiloh, Illinois, United States
• University of Kansas Cancer Center — Kansas City, Kansas, United States
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
• University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
• Siteman Cancer Center at Saint Peters Hospital — City of Saint Peters, Missouri, United States
• Siteman Cancer Center at West County Hospital — Creve Coeur, Missouri, United States
• University of Kansas Cancer Center - North — Kansas City, Missouri, United States
• University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States
• University of Kansas Cancer Center at North Kansas City Hospital — North Kansas City, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Siteman Cancer Center-South County — St Louis, Missouri, United States
• Siteman Cancer Center at Christian Hospital — St Louis, Missouri, United States
• NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center — New York, New York, United States
• Wake Forest Baptist Health - Wilkes Medical Center — Wilkesboro, North Carolina, United States
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
• Vanderbilt Breast Center at One Hundred Oaks — Nashville, Tennessee, United States
• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
• University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States

Full record on ClinicalTrials.gov

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