Clinical trial NCT04159818: Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients
Official title: Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients: the TONIC-2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Triple negative
Metastatic disease
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-11-12
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients are randomized between experimental cohorts and a control cohort.
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Progression free survival
timeFrame: assessed monthly until progression or date of death; median 12 months
Secondary outcomes:
measure: Overall response rate
timeFrame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
measure: Clinical benefit rate
timeFrame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
measure: Overall survival
timeFrame: assessed monthly until date of death; median 12 months
measure: Toxicity of all study regimens
timeFrame: assessed until 100 days after of treatment end
measure: Progression Free Survival after 6 cycles
timeFrame: time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
Study officials:
affiliation: NKI-AvL
name: Marleen Kok, MD
role: PRINCIPAL_INVESTIGATOR
References: