Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Cisplatin

Nivolumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

metronomic schedule, 50mg daily orally for 2 weeks

nivolumab 3 mg/kg, every 2 weeks after induction treatment

Radiation therapy

Low dose doxorubicin

metronomic schedule, 50 mg daily orally for 2 weeks

Marleen Kok, MD

This is a single center non-blinded randomized non-comparative phase II trial. The first stage of the trial consists of five arms ( with induction treatment followed by nivolumab, 1 with no induction treatment before nivolumab).

For the second stage, the number of arms will be reduced based on the results obtained in the first stage.

Triple negative breast cancer (TNBC) patients have a relatively high relapse rate and upon relapse the median overall survival is less than a year. No targeted therapies are currently available for this subgroup. Compared to other breast cancer subtypes, the percentage of tumor-infiltrating lymphocytes (TILs) is significantly higher in TNBC. Given the durable responses induced by the immune checkpoint inhibitor nivolumab in other advanced solid cancers, immunotherapeutic approaches, such as blockade of PD-1 by nivolumab may be the key to treat TNBC. Moreover, since classical anticancer agents can stimulate immune effector cells, the investigators hypothesize that short-term induction treatment with radiation, doxorubicin, cyclophosphamide or cisplatin induces an anticancer immune response resulting in synergistic activity with nivolumab.

Nivolumab After Induction Treatment in Triple-negative Breast Cancer (TNBC) Patients

Adaptive Phase II Randomized Non-comparative Trial of Nivolumab After Induction Treatment in Triple-negative Breast Cancer (TNBC) Patients: TONIC-trial

Time from randomization todate of first tumor progression

complete response or partial response at 12 weeks and 6 months

Beneficial response (complete response, partial response or stable disease) at 6 months

adverse events will be graded according to NCI Common Toxicity Criteria v 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nivolumab After Induction Treatment in Triple-negative Breast Cancer (TNBC) Patients	NCT02499367	Breast Cancer	Nivolumab Radiation thera... Low dose doxoru... Cyclophosphamid... Cisplatin	18 Years -	The Netherlands Cancer Institute
Nivolumab After Induction Treatment in Triple-negative Breast Cancer (TNBC) Patients	NCT02499367	Breast Cancer	Nivolumab Radiation thera... Low dose doxoru... Cyclophosphamid... Cisplatin	18 Years -	The Netherlands Cancer Institute

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