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

Metastatic Breast Cancer Clinical Trial

— TONIC-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04159818
• Other study ID #: N19TON
• Status: Recruiting
• Phase: Phase 2
• Start date: February 21, 2020
• Est. completion date: December 15, 2026

Study information

• Verified date: March 2022
• Source: The Netherlands Cancer Institute
• Contact: Marleen Kok, MD
• Phone: +3120 512
• Email: m.kok[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: December 15, 2026
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Netherlands	Antoni van Leeuwenhoek	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Time from randomization to date of first tumor progression	assessed monthly until progression or date of death; median 12 months
Secondary	Overall response rate	complete response or partial response according to iRECIST and RECIST1.1	assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
Secondary	Clinical benefit rate	Beneficial response (complete response, partial response or stable disease) according to RECIST 1.1 and iRECIST	assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
Secondary	Overall survival	time from nivolumab initiation to death from any cause	assessed monthly until date of death; median 12 months
Secondary	Toxicity of all study regimens	adverse events will be graded according to NCI Common Toxicity Criteria v 5.0	assessed until 100 days after of treatment end
Secondary	Progression Free Survival after 6 cycles	the number of patients free of progression after 6 cycles of nivolumab	time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months