Trial, to evaluate the efficacy and safety of nal-IRI for progressing brain metastases in patients with HER2-negative breast cancer

Phase 1

• Conditions: Progressing brain metastases in patients with HER2-negative breast cancer.; MedDRA version: 19.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002689-30-ES
• Lead Sponsor: Medica Scientia Innovation Research (MedSIR ARO)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-04
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 <2.
9. Life expectancy >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

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified