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

Netherlands Cancer Institute (NKI) logo

Netherlands Cancer Institute (NKI)

Status and phase

Enrolling
Phase 2

Conditions

Metastatic Breast Cancer

Treatments

Drug: Nivolumab
Drug: Low dose doxorubicin
Drug: Cisplatin

Study type

Interventional

Funder types

Other
Industry

Identifiers

Details and patient eligibility

About

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

Full 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.

Enrollment

52 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

52 participants in 3 patient groups

Control group
Experimental group
Description:
no induction treatment, nivolumab 240 mg flat-dose, every 2 weeks
Treatment:
Drug: Nivolumab
Cisplatin induction
Experimental group
Description:
Cisplatin 40mg/m2, weekly for two weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks
Treatment:
Drug: Nivolumab
Drug: Cisplatin
Low dose doxorubicin induction
Experimental group
Description:
Low dose doxorubicin 15mg flat dose, weekly for 8 weeks, after 2 weeks followed by nivolumab 240 mg flat-dose, every 2 weeks
Treatment:
Drug: Nivolumab
Drug: Low dose doxorubicin

Trial contacts and locations

1

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Central trial contact

Marleen Kok, MD; Leonie Voorwerk, MD

Data sourced from clinicaltrials.gov

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