Phase II Study of the Combination of Liposomal Irinotecan (Nal-IRI) and Pembrolizumab for Triple-Negative Breast Cancer (TNBC) With Brain Metastases (BM)

Washington University School of Medicine0 sitesJuly 31, 2023

ConditionsTriple Negative Breast Cancer Brain Metastases

InterventionsPembrolizumab Liposomal Irinotecan

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Triple Negative Breast Cancer
Sponsor: Washington University School of Medicine
Primary Endpoint: Central Nervous System Disease Control Rate (DCR)
Status: Withdrawn
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The study is a phase II with safety lead in, single arm, study using Nal-IRI in combination with pembrolizumab. Nal-IRI will be given IV every 2 weeks starting at 50mg/m2. Pembrolizumab will be given 400mg IV every 6 weeks. Treatment will continue until progression, intolerable side effects or patient/doctor decision to discontinue treatment.

Registry

clinicaltrials.gov

Start Date

July 31, 2023

End Date

January 31, 2030

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Washington University School of Medicine

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject must meet all of the following applicable inclusion criteria to participate in this study:
•Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
•Age ≥ 18 years at the time of consent.
•ECOG Performance Status of 0-1 within 28 days prior to registration.
•Histological or cytological confirmation of triple-negative breast cancer (TNBC) NOTE: TNBC will be defined as expression of ER\<10%, PR\< 10% and HER2 negative either by IHC (0, 1+ are negative, 2+ equivocal) or in situ hybridization method (ratio \<2.0 is negative). AJCC, 8th edition.
•Subjects must have brain metastasis; new or progressive with at least one lesion ≥ 5 mm in at least one dimension. NOTE: the number of brain lesions is not limited.
•Measurable disease according to RECIST 1.1 and/or RANO-BM within 28 days prior to registration.
•Prior treatment with immunotherapy is allowed. Patients CANNOT have received prior liposomal irinotecan or irinotecan. Patients who received prior sacituzumab govitecan are eligible if without disease progression for at least 16 weeks on therapy and a washout of at least 24 weeks prior to C1D
•NOTE: No more than 4 prior lines of therapy in the metastatic setting is allowed.
•Prior cancer treatment including investigational agents must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.

Exclusion Criteria

•Subjects meeting any of the criteria below may not participate in the study:
•Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: No HIV testing is required unless mandated by local health authority.
•Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
•Has a known history of active TB (Bacillus Tuberculosis).
•Has an active infection requiring systemic therapy.
•Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
•Has received colony-stimulating factors (e.g., granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony stimulating factor \[GM-CSF\]) within 2 weeks prior to the first dose of study drug.
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to C1D
•Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
•Has had an allogenic tissue/solid organ transplant.

Arms & Interventions

Pembrolizumab + Liposomal Irinotecan

* 400 mg of pembrolizumab intravenously on Day 1 of each Cycle (Cycle is 42 days) * 50 mg/m\^2 of liposomal irinotecan (Nal-IRI) intravenously every 2 weeks of each Cycle (Cycle is 42 days)

Intervention: Pembrolizumab

Pembrolizumab + Liposomal Irinotecan

* 400 mg of pembrolizumab intravenously on Day 1 of each Cycle (Cycle is 42 days) * 50 mg/m\^2 of liposomal irinotecan (Nal-IRI) intravenously every 2 weeks of each Cycle (Cycle is 42 days)

Intervention: Liposomal Irinotecan

Outcomes

Primary Outcomes

Central Nervous System Disease Control Rate (DCR)

Time Frame: 6 months

-DCR is defined as the rate of complete response (CR) + rate of partial response (PR), and rate of stable disease (SD) at 6 months and will be determined as per modified Neuro-Oncology-Brain Metastases (RANO-BM) criteria

Secondary Outcomes

Safety and tolerability as measured by the number of grade 3 and 4 adverse events(Through 90 days after completion of treatment (estimated to be 9 months))
Central Nervous System Objective Response Rate (ORR)(Through completion of treatment (estimated to be 6 months))
Non-Central Nervous System Objective Response Rate (ORR)(Through completion of treatment (estimated to be 6 months))
Progression Free Survival (PFS)(Through completion of follow-up (estimated to be 3 years and 6 months))
Overall Survival (OS)(Through completion of follow-up (estimated to be 3 years and 6 months))