Study Stopped
Inadequate accrual rate
Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Maintenance Treatment (Trastuzumab and Pertuzumab) After Initial Chemotherapy in a Phase Ib/II Trial for Advanced HER2 Positive Breast Cancer
Phase Ib/II Trial of Copanlisib in Combination With Trastuzumab and Pertuzumab After Induction Treatment of HER2 Positive (HER2+) Metastatic Breast Cancer (MBC) With PIK3CA Mutation or PTEN Mutation
4 other identifiers
interventional
2
1 country
5
Brief Summary
This phase Ib/II trial studies the side effects and best dose of copanlisib when given together with trastuzumab and pertuzumab and to see how well they work after induction treatment in treating patients with HER2 positive stage IV breast cancer with PIK3CA or PTEN mutation. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may kill tumor cells that are left after chemotherapy. The addition of copanlisib to the usual treatment (trastuzumab and pertuzumab) could shrink the cancer or stabilize it for longer duration as compared to the usual treatment alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2021
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 27, 2019
CompletedFirst Posted
Study publicly available on registry
September 30, 2019
CompletedStudy Start
First participant enrolled
May 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 29, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 29, 2022
CompletedResults Posted
Study results publicly available
June 27, 2024
CompletedOctober 1, 2025
September 1, 2025
11 months
September 27, 2019
January 11, 2024
September 12, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Safety run-in Phase 1b/2
Incidence of adverse events and serious adverse events to determine safety: incidence of DLTs to determine RP2D
21 days
Incidence of Dose Limiting Toxicities (DLTs) (Phase Ib)
21 days
Progression-free Survival (PFS) (Phase II)
12 months
Secondary Outcomes (4)
Progression-free Survival (Phase Ib)
12 months
Overall Survival (OS) (Phase Ib)
12 months
Overall Survival (OS) (Phase II)
12 months
Incidence of Adverse Events and Serious Adverse Events (Phase II)
12 months
Study Arms (2)
Phase I, Phase II Arm I (copanlisib, trastuzumab, pertuzumab)
EXPERIMENTALPatients receive copanlisib IV over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Phase II Arm II (trastuzumab, pertuzumab)
ACTIVE COMPARATORPatients receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Phase 1B: Any prior number of lines of therapy in metastatic setting is allowed, provided patients are considered candidates for trastuzumab and pertuzumab combination or on maintenance trastuzumab and pertuzumab (with or without prior chemotherapy) as long as dose limiting toxicity (DLT) can be determined. For Phase 2:Patients should have only received first line of induction chemotherapy (taxane) with trastuzumab and pertuzumab in the metastatic setting
- Presence of actionable mutation in either PIK3CA or PTEN on molecular testing
- For Phase 2-Patients must be within 8 weeks of completion of first-line induction chemotherapy (i.e., 4-8 cycles of any taxane, trastuzumab and pertuzumab) without evidence of progression. Patients may receive up to 2 doses of HER2 targeted treatment between end of induction treatment and start of trial, while eligibility is being confirmed
- Clinical stage IV as assessed by American Joint Committee on Cancer (AJCC) (8th edition, anatomic staging) guidelines with known metastatic disease (Edge and Compton, 2010; Amin et al., 2017)
- HER2+ breast cancer patients with any ER/PR status as assessed by the American Society of Clinical Oncology (ASCO)-College of American Pathologists (ASCO-CAP) guidelines (Wolff et al., 2013; Wolff et al., 2018). HER2 testing of metastasis will be required
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
- Absolute neutrophil count (ANC) \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 9 g/dL
- Left ventricular ejection fraction (LVEF) \>= 50% by echocardiogram or multigated acquisition scan (MUGA)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN OR =\< 5 x ULN for subjects with liver metastases
- Creatinine =\< 1.5 x institutional ULN OR measured or calculated creatinine clearance \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]). Creatinine clearance should be calculated per institutional standard
- International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulation as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless patient is receiving anticoagulation as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- +6 more criteria
You may not qualify if:
- Known active hepatitis B or hepatitis C infection. All patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to study drug start using the routine hepatitis virus lab panel. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on non-CYP3A4-interactive suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV ribonucleic acid (RNA)
- Human immunodeficiency virus (HIV)-positive patients, unless they have CD4 counts \> 500 cells/mm\^3 in the past 6 months and do not require CYP3A4-interactive antiretroviral therapy
- Active infection requiring IV antibiotics or other uncontrolled intercurrent illness requiring hospitalization
- Inability to comply with the study and follow-up procedures
- History of cerebrovascular accident (CVA), myocardial infarction, symptomatic congestive heart failure, cardiac arrhythmia, or unstable angina within the previous 6 months before starting therapy
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the following exceptions: alopecia (any grade is acceptable); neuropathy must have resolved to =\< grade 2. Congestive heart failure (CHF) due to prior anti-cancer therapy must have been =\< grade 1 in severity at the time of occurrence, and must have resolved completely
- Current uncontrolled hypertension (\>= 150/90)
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Patients with uncontrolled type I or II diabetes mellitus (DM); uncontrolled DM is defined as glycosylated hemoglobin (HbA1c) \> 8.5% and a fasting blood glucose of \> 120 mg/dL within 14 days prior to trial entry
- Immunosuppressive therapy is not allowed while on study
- Patients who are receiving any other investigational agents
- Patients with leptomeningeal disease or active untreated brain metastases
- Prior exposure to any PI3K, AKT or mTOR inhibitors. History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, or HER2 inhibitors
- 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:
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
Los Angeles County-USC Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Senthil Damodaran, MD. PhD.
- Organization
- University of Texas M D Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Senthilkumar Damodaran
University of Texas MD Anderson Cancer Center LAO
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
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 27, 2019
First Posted
September 30, 2019
Study Start
May 20, 2021
Primary Completion
April 29, 2022
Study Completion
April 29, 2022
Last Updated
October 1, 2025
Results First Posted
June 27, 2024
Record last verified: 2025-09
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.