A Phase 2 interventional study of Irinotecan (CPT-11) liposome in Breast Cancer Metastatic, sponsored by MedSIR. Completed at 16 sites in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-23.
Sponsored by MedSIR · Phase 2, Interventional, and Treatment
Multicenter open-label, phase II trial, to evaluate the efficacy and safety of nal-IRI in patients with HER2-negative breast cancer, who have documented Central Nervous System (CNS) progression following Whole Brain Radio Therapy (WBRT), Stereotactic Radiosurgery (SRS) and/or surgery, as determined by the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial, with the primary objective of assessing the efficacy of nal-IRI single agent in a cohort of HER2-negative metastatic breast cancer (MBC) patients with CNS involvement.
Eligible patients will have histologically proven diagnosis of adenocarcinoma of the breast, they must have progressed to at least one prior chemotherapy regimen in the metastatic setting and must have been progressed in CNS to previous local treatment (Surgery and/or WBRT and/or SRS) showing at least one measurable lesion in the CNS (symptomatic meningeal carcinomatosis is not permitted). Eligible patients must have been previously received at least treatment with taxanes (either in the neo/adjuvant or in the metastatic scenario). Patients could not be eligible if they are candidates for a local treatment with a radical intention.
Patients will be accrued in a two-stage design. Considering a drop-out rate of 10%, the accrual goal will be a total of 63 patients in both stages (first stage will include 23 evaluable patients and the second stage will include 33 more evaluable patients).
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.
Exclusion Criteria:
This is a single arm study. After signing the informed consent form, patients will start treatment with nal-IRI. nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy.
Drug: Irinotecan (CPT-11) liposome
nal-IRI (nanoliposomal irinotecan, also known as MM-398 and PEP02) is irinotecan free base, (also known as CPT-11) a topoisomerase 1 inhibitor, encapsulated in a liposome drug delivery system. nal-IRI will be administered 50 mg/m2 on D1 of a 14-day cycle in monotherapy.
Also known as: nal-IRI
CNS Overall Response Rate (ORR)
The efficacy of nal-IRI will be measured in terms of CNS ORR, defined as per RANO-BM criteria. According to these criteria 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. Partial Response (PR) will be defined as a decrease of at least 30% in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD, sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically.
Time frame: From Baseline up to 80 weeks after patient entry
CNS disease stabilization on week 12
CNS clinical benefit rate (CBR) at week 12 will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 12 weeks assessed by the modified Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) criteria.
Time frame: From Baseline up to 12 weeks after patient entry
ORR, according to a volumetric parameter, and to the RECIST v.1.1 criteria
ORR according to a volumetric parameter. For this objective, PR will be defined as \> 65% volumetric reduction of CNS lesion(s) and to the RECIST v.1.1 criteria. The volumetric parameter will be centrally reviewed.
Time frame: From Baseline up to 80 weeks after patient entry
CBR
The percentage of patients who experience a CR, PR or SD for at least 24 weeks and assessed by the RECIST v.1.1 criteria.
Time frame: 3 years
Safety profile of nal-IRI in this population by Common Terminology Criteria for Adverse Events version 4 (CTCAE v.4) criteria
This study will consider the National Cancer Institute (NCI) CTCAE v.4 criteria grade 3 and 4 adverse events (AEs) and serious AEs (SAEs) in order to assess the safety and tolerability objectives.
Time frame: 3 years
Progression-Free Survival (PFS)
PFS will be defined as the time from the first dose of treatment to death or disease progression as assessed by the Investigator per RECIST v1.1 criteria.
Time frame: 3 years
Overall Survival (OS)
OS will be defined as the time from the first dose of treatment to death for any cause.
Time frame: 3 years
Disease Control Rate
DCR will be defined as the percentage of patients who experience a CR, PR or stable disease determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Time frame: 18 months after last patient included
TTR
TTR will be defined as the time from treatment initiation to time of the first objective tumor response observed in patients who achieved a CR or PR, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Time frame: From treatment initiation to time of the first objective tumor response in patients with CR or PR,
DoR
DoR will be defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Time frame: time from the first occurrence of a documented objective response to disease progression or death
MTS
MTS from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease observed, determined locally by the investigator, using RANO-BM criteria (for IC lesions) and RECIST criteria v.1.1 (for IC, EC, and overall lesions) in patients with progressing brain metastases and in all patients with CNS involvement.
Time frame: From baseline
Plan to share: No — It is not planned
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