Progressing brain metastases in patients with HER2-negative breast cancer. MedDRA version: 19.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ONIVYDE
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: irinotecan hydrochloride trihydrate (salt in a pegylated liposomal formulation)
Other descriptive na
Sponsors
Medica Scientia Innovation Research (MedSIR ARO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female or male patients > 18 years 2. Patients must have a diagnosis of metastatic breast cancer. 3. Patients should have been pretreated with taxanes at any time prior to the study enrolment if not formally contraindicated. 4. At least one prior chemotherapy regimen for advanced disease. 5. Evidence of new and/or progressive brain metastases following previous WBRT and/or SRS and/or surgery. 6. At least one brain lesion needed to be measurable (=10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging). 7. HER2 negative breast cancer defined as 0 - 1+ by immunohistochemistry or FISH negative result. 8. ECOG performance status 12 weeks. 10. Patients must have sufficient organ and marrow function as defined below: a. Hematopoietic parameters: i. Absolute neutrophil count = 1,5 x 109/L ii. Platelets = 100 x 109/L iii. Haemoglobin = 9 mg/dL b. Hepatic parameters:i. Total bilirubin = 1.5 mg/dL ii. AST (SGOT)/ALT (SGPT) = 2.5 X institutional upper limit of normal c. Renal parameters: i. Creatinine = 1.5 X institutional upper limits of normal, OR ii. Creatinine clearance = 60 mL/min/1.73 m2 for pts w/ creatinine levels > institutional normal. 11. Participants of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation as well as a negative serum pregnancy test within 7 days of study enrolment. 12. Ability to understand and the willingness to sign a written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: 1. Patients must not have previously received nal-IRI or any other form of irinotecan, conventional or liposomal. 2. Patients who have received prior anti-cancer treatment with chemotherapy, endocrine therapy, immunotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to starting study treatment. 3. Radiation therapy encompassing more than 30% of bone marrow. 4. Significant chronic gastrointestinal disorder with diarrhea as a major symptom (i.e Crohn’s disease, ulcerative colitis, malabsorption, or grade = 2 diarrhea of any etiology at baseline) 5. Have a serious concomitant systemic disorder (e.g. active infection including HIV, or cardiac disease) incompatible with the study (at the discretion of investigator), previous history of bleeding diathesis, or treatment with Sintrom. 6. Patients who have symptomatic lymphangitis, dyspnoea at rest or meningeal carcinomatosis. (Patients with asymptomatic involvement may be enrolled in the study.) 7. Patients must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy or other therapy intended for the treatment of breast cancer. For peripheral neuropathy, up to CTCAE (v4.0) Grade 2 is acceptable for patients with pre-existing condition. 8. Patients may not be receiving any other investigational or anticancer agents while on the study. 9. History of other malignancies, which could affect compliance with the protocol or interpretation of the results. Patients with malignancies diagnosed more than 5 years prior to study day 1, adequately treated carcinoma in situ of the cervix or basal or squamous cell skin are generally eligible. 10. Pregnant or lactating women. 11. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings. 12. Active infection or an unexplained fever >38.5°C (excluding tumoral fever), which in the physician’s opinion might compromise the patient’s health. 13. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study. 14. Current use or any use in the last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors 15. Known hypersensitivity to any of the components of nanoliposomal irinotecan (nal-IRI) other liposomal irinotecan formulations or irinotecan.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of nal-IRI in patients with HER2- negative metastatic breast cancer who have documented CNS progression following WBRT, SRS and/or surgery, as determined by the RANO-BM criteria;Secondary Objective: -To determine the rate of CNS disease stabilization on week 12. -To determine the objective response rate, according to a volumetric parameter and to RECIST 1.1 criteria. -Clinical benefit rate (total number of objective responses plus stable disease lasting at least 12 weeks). -Safety and tolerability (by CTCAE v4 criteria). -Median progression-free survival (PFS). -Median overall survival (OS).;Primary end point(s): Central Nervous System Overall Response Rate (ORR) per the RANO-BM criteria.;Timepoint(s) of evaluation of this end point: Complete response (CR) will be defined as the disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions, no corticosteroids; stable or improved clinically. We will describe number and proportion of patients with CNS overall response in first stage and total sample. We will estimate the proportion of responders with the 95% Pearson-Clopper confidence intervals. We will estimate the uniformly minimum variance unbiased estimator (UMVUE), p-value and 95% confidence interval | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CNS CBR at 12w ORR Clinical Benefit Rate (CBR) Safety Median progression-free survival (PFS) Median overall survival (OS);Timepoint(s) of evaluation of this end point: Within 12 weeks. | — |
Countries
Spain
Contacts
Public ContactProject Manager
Medica Scientia Innovation Research (MedSIR ARO)
Outcome results
None listed