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Combination Liposomal Irinotecan and Pembrolizumab For Triple-Negative Breast Cancer (TNBC) With Brain Metastases (BM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05255666
Recruitment Status : Recruiting
First Posted : February 24, 2022
Last Update Posted : June 2, 2022
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Cynthia Ma, Hoosier Cancer Research Network

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.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Brain Metastases Drug: Pembrolizumab Drug: Liposomal Irinotecan Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of The Combination of Liposomal Irinotecan (Nal-IRI) and Pembrolizumab For Triple-Negative Breast Cancer (TNBC) With Brain Metastases (BM)
Actual Study Start Date : May 24, 2022
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Experimental Group

400 mg of Pembrolizumab intravenously on Day 1 of each Cycle (Cycle is 42 days)

50 mg/m2 of Nal-IRI intravenously on Day 1, Day 15, and Day 29 of each Cycle (Cycle is 42 days)

Drug: Pembrolizumab
400 mg intravenously
Other Name: Keytruda

Drug: Liposomal Irinotecan
50 mg/m2 intravenously
Other Name: NaI-IRI

Primary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: 6 months ]
    Assess the Central Nervous System (CNS) disease control rate (DCR) at 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 Outcome Measures :
  1. Assess adverse events [ Time Frame: 4 months ]
    Assess the safety and tolerability of the study regimen. Safety and tolerability is defined by Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5

  2. CNS Objective Response Rate (ORR) [ Time Frame: 3 years ]
    Assess CNS objective response rate (ORR). CNS ORR will include CNS complete response (CR) + partial response (PR) and will be determined as per modified RANO-BM criteria.

  3. Objective Response Rate (ORR) [ Time Frame: 3 years ]
    Assess non-CNS ORR. Non-CNS ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST 1.1

  4. Progression Free Survival (PFS) [ Time Frame: 3 years ]
    Assess progression-free survival (PFS). PFS is defined as the time from Day 1 of treatment until the criteria for disease progression is met as defined by RECIST 1.1 and/or RANO-BM or death as a result of any cause.

  5. Overall Survival [ Time Frame: 3 years ]
    Assess overall survival (OS). OS is defined as the time from Day 1 of treatment until death as a result of any cause.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 C1D1. 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.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.

    • Hematological

      • Absolute Neutrophil Count (ANC): ≥ 1.5 K/mm3
      • Hemoglobin (Hgb): ≥ 9 g/dL; without erythropoietin dependency and without packed red blood cell (PRBC) transfusion within 2 weeks of registration
      • Platelet Count (PLT): ≥100 000/µL
    • Renal

      • Creatinine OR: ≤1.5 × ULN OR
      • Calculated creatinine clearance: ≥30 mL/min
    • Hepatic

      • Total Bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
      • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
      • Albumin: > 30 g/L
    • Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Life expectancy of ≥ 12 weeks as assessed by the investigator.
  • Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception as outlined in the protocol.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

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 C1D1.
  • 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.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Is pregnant or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05255666

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Contact: Cynthia Ma, MD, PhD 314-362-9383
Contact: Rae Richards 317-634-5842 ext 38

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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Catherine Sueme    314-747-7991   
Principal Investigator: Cynthia Ma, MD, PhD         
Sponsors and Collaborators
Cynthia Ma
Merck Sharp & Dohme LLC
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Principal Investigator: Cynthia Ma, MD, PhD Washington University School of Medicine
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Responsible Party: Cynthia Ma, Sponsor Investigator, Hoosier Cancer Research Network Identifier: NCT05255666    
Other Study ID Numbers: HCRN BRE20-442
First Posted: February 24, 2022    Key Record Dates
Last Update Posted: June 2, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action