previously treated HER2+ advanced PIK3CA mutated breast cancer
Conditions
Interventions
Trastuzumab: 1 intravenous administration (8 mg/kg) as an initial higher dose
on day 1, and then 1 intravenous administration (6 mg/kg ) every 3 weeks, or 1
intravenous administration (4 mg/kg) as a
Sponsors
GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Written informed consent prior to any specific study procedures, showing patient willingness to comply with all study procedures. 2.Histologically or cytologically documented locally recurrent inoperable or metastatic breast cancer with HER2+ status based on local laboratory determination, preferably on the most recent available FFPE tumor sample, and according to American Society of Clinical Oncology (ASCO)/Collegue of American Pathologists (CAP) international guidelines valid at the time of the assay. In case of discordance in HER2+ status in different biopsies, the result from the most recent biopsy will be used. 3.Documented HR status based on local laboratory, preferably on the most recent available FFPE tumor sample, and according to ASCO/CAP international guidelines valid at the time of the assay. In case of discordance in HR status in different biopsies, the result from the most recent biopsy will be used. HR+ will be defined as >=1% positive cells by immunohistochemistry for Estrogen Receptor (ER) and/or Progesterone Receptor (PgR). HR- will be defined as = 12 weeks. 12.Adequate organ and marrow function defined as follows: -Absolute neutrophil count (ANC) >= 1,500/mm3 (1.5x109/L). -Platelets >= 100,000/mm3 (100x109/L). -Hemoglobin >= 9g/dL (90g/L). -Calcium (corrected for serum albumin) and magnesium within normal limits or = 35 mL/min using Cockcroft-Gault formula (if creatinine is >=1.5 ULN). -Total bilirubin < 2 x ULN (any elevated bilirubin should be asymptomatic at enrollme
Exclusion criteria
Exclusion criteria: 1.Have recently received study agent(s) in any of the following scenarios: -Fulvestrant within 12 months prior to the start of the study treatment (HR+ cohort only). -All the chemotherapy options, vinorelbine, capecitabine and eribulin within 12 months prior to start the study treatment. Patients that have received one or more of these chemotherapies more than 12 months prior can receive them again as study therapy. 2.Symptomatic visceral disease or any disease burden that makes the patient ineligible for experimental therapy per the investigator*s best judgment. 3.Symptomatic central nervous system (CNS) metastases. However, patients with CNS metastases who have been adequately treated, are asymptomatic and do not require corticosteroid or anti-epileptic medication are eligible. 4.Presence of leptomeningeal carcinomatosis. 5.Other invasive malignancy (different from the current breast cancer) at the time of enrollment or previous diagnosis of a completely removed malignancy within 3 years prior to randomization except for adequately treated (including complete surgical removal) of International Federation of Gynecology and Obstetrics (FIGO) stage I grade 1 endometrial cancer, basal or squamous cell carcinoma of the skin, thyroid cancer limited to thyroid gland, in situ carcinoma of the cervix, and grade 1-2 early stage bladder cancer defined as T1 or less, without nodal involvement (N0). 6.Patients with an established diagnosis of diabetes mellitus type I or not controlled type II (FPG >= 140 mg/dL [7.7 mmol/L] or HbA1c >= 6.5%), or history of gestational diabetes (as per ACOG guidelines) or documented steroid-induced diabetes mellitus. 7.Prior treatment with any mTOR, AKT or PI3K inhibitor. 8.Patients treated within the last 7 days prior to treatment initiation with: -Drugs that are strong inducers of CYP3A4. -Drugs that are inhibitors of BCRP (Breast Cancer Resistance Protein). 9.Patients who received before randomization: -Any investigational agent or other anti-cancer therapy not listed in the protocol within 4 weeks prior to starting study treatment (all acute toxic effects, including peripheral neurotoxicity must be resolved to NCI-CTCAE version 5.0 grade 25% of bone marrow are not eligible regardless of when it was administered. -Major surgery within 4 weeks prior to starting study treatment and/or if patient has not recovered from major side effects. 10.Patient has clinically significant, uncontrolled heart disease and/or recent cardiac events. 11.Bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting factor deficiency) or lon
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS: Time from randomization to objective disease progression based on the investigator*s assessment according to the response evaluation criteria for solid tumors (RECIST) version 1.1., or death from any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| OS: time from randomization to death from any cause. OR: complete or partial response as best overall response based on the investigator*s assessment according to RECIST version 1.1. Safety and tolerability: adverse events (AEs) grades will be defined by the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0. AE terms will be coded according to the MedDRA dictionary. | — |
Countries
Netherlands
Outcome results
None listed