Evaluation of the Efficacy and Safety of Nal-IRI for Progressing Brain Metastases in Breast Cancer Patients

NCT03328884 | Completed Phase 2

• 2 other identifiers: MedOPP1072016-002689-30
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Breast Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• 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.

  From Baseline up to 80 weeks after patient entry

Secondary Outcomes (10)

• CNS disease stabilization on week 12

  From Baseline up to 12 weeks after patient entry

• ORR, according to a volumetric parameter, and to the RECIST v.1.1 criteria

  From Baseline up to 80 weeks after patient entry

• CBR

  3 years

• Safety profile of nal-IRI in this population by Common Terminology Criteria for Adverse Events version 4 (CTCAE v.4) criteria

  3 years

• Progression-Free Survival (PFS)

  3 years

Study Arms (1)

nal-IRI

OTHER

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

Interventions

Irinotecan (CPT-11) liposome DRUG

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

nal-IRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patients \> 18 years
• Patients must have a diagnosis of metastatic breast cancer.
• Patients should have been pretreated with taxanes at any time prior to the study enrolment if not formally contraindicated.
• At least one prior chemotherapy regimen for advanced disease.
• Evidence of new brain metastases and/or stable or progressive brain metastases following previous WBRT and/or SRS and/or surgery.
• At least one brain lesion needed to be measurable for new and progressive metastases (≥10 mm on T1-weighted, gadolinium-enhanced magnetic resonance imaging). For stable brain metastases at least one extracerebral lesion need to be measurable.
• HER2 negative breast cancer defined as 0 - 1+ by immunohistochemistry or FISH negative result.
• ECOG performance status \<2.
• Life expectancy \>12 weeks.
• 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.
• Participants of childbearing potential must agree to use at least efficient contraception method (even though it is recommendable for them to use a highly effective method) 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 and at the end of treatment visit.
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Patients must not have previously received nal-IRI or any other form of irinotecan, conventional or liposomal.
• 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.
• Radiation therapy encompassing more than 30% of bone marrow.
• 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)
• 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.
• Patients who have symptomatic lymphangitis, dyspnoea at rest or meningeal carcinomatosis. (Patients with asymptomatic involvement may be enrolled in the study.)
• 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.
• Patients may not be receiving any other investigational or anticancer agents while on the study.
• 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.
• Pregnant or lactating women.
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings.
• Active infection or an unexplained fever \>38.5°C (excluding tumoral fever), which in the physician's opinion might compromise the patient's health.
• Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.
• Current use or any use in the last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
• Known hypersensitivity to any of the components of nanoliposomal irinotecan (nal-IRI) other liposomal irinotecan formulations or irinotecan.

Sponsors & Collaborators

• MedSIR: lead

Study Sites (16)

ICO

Badalona, Spain

Location

IOB Institute of Oncology - Quirón Barcelona

Barcelona, Spain

Location

Hospital Universitario Virgen de Las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Clinico San Cecilio

Granada, 18016, Spain

Location

H. Ruber Juan Bravo

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Doce de Octubre

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

MD Anderson Madrid

Madrid, Spain

Location

Hospital Clínico Virgen de la Victoria

Málaga, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

Son Llatzer

Palma de Mallorca, Spain

Location

Sant Joan de Reus

Reus, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

IVO

Valencia, Spain

Location

H. Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Interventions

Irinotecan; Liposomes; irinotecan sucrosofate

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials

Study Officials

• Javier Cortes

  Hospital Universitario Ramon y Cajal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an international, prospective, open-label, multicenter, single arm, two-stage Simon Design phase II clinical trial

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: November 1, 2017
• Study Start: May 2, 2017
• Primary Completion: August 31, 2018
• Study Completion: April 2, 2025
• Last Updated: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (16)