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
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.
• 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
• Patients with treated brain metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
• Patients who are therapeutically treated with anticoagulation including warfarin will be allowed to participate provided that their medication dose and INR/PTT is stable. Due to interaction of copanlisib with warfarin, patients who are on warfarin should be monitored closely while on this trial
• Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (\>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study
• Patients and their partners, if sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 7 months after last dose of study drug(s) to prevent pregnancy in the study patient or partner
• Hormone receptor positive (ER+ and / PR+) breast cancer patients will be allowed to continue endocrine therapy as clinically indicated while participating in the study.
• Ability to understand and the willingness to sign a written informed consent document