UNRESECTABLE LOCALLY ADVANCED OR METASTATIC RIPLE-NEGATIVE BREAST CANCER PATIENTS MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classificatio
Conditions
Interventions
Product Name: Ipatasertib
Product Code: GDC-0068
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IPATASERTIB
Current Sponsor code: GDC-0068
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Medica Scientia Innovation Research S.L (MEDSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed TNBC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criterio based on local testing on the most recent analyzed biopsy. Triplenegative is defined as 3.0 x 109/L, absolute neutrophil count (ANC) > 1.5 x 109/L, platelet count >100.0 x109/L, and hemoglobin > 9.0 g/dL. b) Hepatic: Serum albumin = 3 g/dL; Bilirubin = 1.5 times the upper
Exclusion criteria
Exclusion criteria: 1. Previous treatment with PI3K, mTOR, or AKT inhibitors 2. Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (e.g.,radiotherapy, stereotactic surgery), are clinically stable, and off anticonvulsants and steroids for at least two weeks before first dose of study treatment. 3. Radiotherapy or limited-field palliative radiotherapy within seven days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade = 1 and/or from whom = 25% of the bone marrow has been previously irradiated. 4. Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 28 days of start of study drug, or patients who have not recovered from the side effects of any major surgery. 5. Grade = 2 peripheral neuropathy. 6. Grade = 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia. 7. History of type I or type II diabetes mellitus either requiring insulin or with a baseline fasting glucose > 150 mg/dL (8.3 mmol/L) or high hemoglobin A1c (HbA1c) as defined as > 7%. Patients who are on a stable dose of oral diabetes medication during at least two weeks prior to initiation of study treatment are eligible for enrolment. 8. Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, spergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia). 9. Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required. 10. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 11. Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) > 480 milliseconds. 12. Patients have an active cardiac disease or a history of cardiac dysfunction. 13. Patients have any of the following cardiac conduction abnormalities: a) Ventricular arrhythmias except for benign premature ventricular contractions. b) Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication. c) Conduction abnormality requiring a pacemaker. d) Other cardiac arrhythmia not controlled with medication. 14. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 14 days or five drug-elimination half-lives, whichever is longer, prior to initiation of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the intention-to-treat (ITT) population of patients with taxanepretreated unresectable locally advanced or metastatic triple-negative breast cancer (TNBC).;Secondary Objective: • To determine the efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the subset of patients with phosphatidylinositol 3-kinase catalytic subunit (PIK3CA)/AKT1/phosphatase and tensin homolog (PTEN)-altered tumors. Exploratory objectives: To determine the efficacy of ipatasertib (GDC-0068) in combination with capecitabine, eribulin, or carboplatin plus gemcitabine in the subset of patients with phosphatidylinositol 3-kinase catalytic subunit (PIK3CA)/AKT1/phosphatase and tensin homolog (PTEN)-altered tumors. • To evaluate predictive or prognostic biomarkers (plasma or tissue) associated with disease activity status or response to treatment. • To identify possible mechanisms of resistance to study treatments through the comparative analysis of potential biomarkers from paired pre-treatment and post-progression tumor and blood samples. ;Primary end point(s): Incidence of adverse events (AEs) as assessed by the investigator, with severity determined through the use of US National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0.;Timepoint(s) of evaluation of this end point: Pending | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-free survival (PFS), defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator through the use of RECIST v.1.1. • Time to response (TTR), defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of = 30%) observed for patients who achieved a complete response (CR) or partial response (PR), as determined locally by the investigator through the use of RECIST v.1.1. • Objective response rate (ORR), defined as a CR or PR as determined locally by the investigator through the use of RECIST v.1.1. • Duration of response (DoR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator through use of RECIST v.1.1. • Clinical benefit rate (CBR), defined as an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined locally by the investigator through the use of RECIST v.1.1. • Overall survival (OS), defined as the time from treatment initiation to death from any cause, as determined locally by the investigator through use of RECIST v.1.1. • Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as determined locally by the investigator through use of RECIST v.1.1. Exploratory endpoints: • PFS, TTR, ORR, DoR, CBR, OS, and best percentage of change in target tumor lesions determined locally by the investigator through the use of RECIST v.1.1 in the subset of patients with PIK3CA/AKT1/PTEN-altered tumors. • Relationship between tissue- and blood-based biomarkers and patient clinical features (e.g., baseline features) and outcome (e.g., duration of PFS). • Changes in mutation and | — |
Countries
Portugal
Contacts
Public ContactMelissa Fernández
Medica Scientia Innovation Research S.L (MEDSIR)
Outcome results
None listed