RecruitingPhase 2NCT04159818

Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients

Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients: the TONIC-2 Trial


Sponsor

The Netherlands Cancer Institute

Enrollment

52 participants

Start Date

Feb 21, 2020

Study Type

INTERVENTIONAL

Conditions

Summary

This is a single center non-blinded randomized multi-cohort non-comparative phase II trial with a Simon's two-stage design.


Eligibility

Min Age: 18 Years

Inclusion Criteria10

  • Metastatic or incurable locally advanced triple negative breast cancer (ER \< 10%, HER2 IHC 0,1+ or 2+ with no amplification)
  • Metastatic lesion accessible for histological biopsy
  • years or older
  • Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease. Treatment with low-dose doxorubicin in the palliative setting is not allowed.
  • WHO performance status of 0 or 1
  • Measurable or evaluable disease according to RECIST 1.1
  • Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year
  • Subjects with brain metastases are eligible if these are not symptomatic and free of progression of at least 4 weeks
  • A maximum dosage of 360 mg/m2 of anthracyclines and no previous anthracycline-related cardiac toxicity. In case of radiation in the cardiac area, hypertension, diabetes mellitus or hypercholesterolemia, the left ventricular ejection fraction must be 50% or higher.
  • Adequate bone marrow, kidney and liver function

Exclusion Criteria8

  • uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
  • known history of leptomeningeal disease localization
  • history of having received other anticancer therapies within 2 weeks of start of the study drug
  • history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (\>10 mgl daily prednisone equivalents) or chronic infections.
  • prior treatment with immune checkpoint inhibitors.
  • active other cancer
  • history of uncontrolled serious medical or psychiatric illness
  • current pregnancy or breastfeeding

Interventions

DRUGNivolumab

240 mg flat-dose, every 2 weeks. From 20 weeks onwards, nivolumab will be administered every 4 weeks with a flat-dose of 480 mg starting from week 20 onwards

DRUGCisplatin

40mg/m2, weekly for two weeks

DRUGLow dose doxorubicin

15mg flat dose, weekly for 8 weeks


Locations(1)

Antoni van Leeuwenhoek

Amsterdam, Netherlands

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NCT04159818


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