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Recruiting NCT04159818

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

Phase II Interventional Metastatic Breast Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Nivolumab, Cisplatin, Low dose doxorubicin.
Who it may be relevant to
Registry conditions: Metastatic Breast Cancer. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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

Detailed description

In the first stage, 13 evaluable patients will be accrued per cohort. Evaluable is defined as: at least one administration of nivolumab and availability of paired biopsies for immunohistochemistry (for induction treatment cohorts pre-induction and pre-nivolumab biopsies).

If there are 1 or no responses observed in these 13 patients, the cohort will be stopped. Otherwise, 21 additional patients will be accrued for a total of 34.

Interventions

  • Drug Nivolumab
    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
  • Drug Cisplatin
    40mg/m2, weekly for two weeks
  • Drug Low dose doxorubicin
    15mg flat dose, weekly for 8 weeks

Primary outcome measures

  • Progression free survival [Time frame: assessed monthly until progression or date of death; median 12 months]
Secondary outcome measures (5)
  • Overall response rate [Time frame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months]
  • Clinical benefit rate [Time frame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months]
  • Overall survival [Time frame: assessed monthly until date of death; median 12 months]
  • Toxicity of all study regimens [Time frame: assessed until 100 days after of treatment end]
  • Progression Free Survival after 6 cycles [Time frame: time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months]

Eligibility criteria

Inclusion criteria

  • 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
  • 18 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 criteria

  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

Netherlands · 1 center
  • Antoni van Leeuwenhoek — Amsterdam

Identifiers

NCT: NCT04159818 · N19TON

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗