Metastatic Breast Cancer
Conditions
Keywords
Triple negative, Metastatic disease
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.
Interventions
DRUGNivolumab
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
DRUGCisplatin
40mg/m2, weekly for two weeks
15mg flat dose, weekly for 8 weeks
Sponsors
Bristol-Myers Squibb
The Netherlands Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Patients are randomized between experimental cohorts and a control cohort.
Intervention model description
Patients are randomized between experimental cohorts and a control cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | assessed monthly until progression or date of death; median 12 months | Time from randomization to date of first tumor progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months | complete response or partial response according to iRECIST and RECIST1.1 |
| Clinical benefit rate | assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months | Beneficial response (complete response, partial response or stable disease) according to RECIST 1.1 and iRECIST |
| Overall survival | assessed monthly until date of death; median 12 months | time from nivolumab initiation to death from any cause |
| Toxicity of all study regimens | assessed until 100 days after of treatment end | adverse events will be graded according to NCI Common Toxicity Criteria v 5.0 |
| Progression Free Survival after 6 cycles | time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months | the number of patients free of progression after 6 cycles of nivolumab |
Countries
Netherlands
Contacts
Primary ContactMarleen Kok, MD
Backup ContactLeonie Voorwerk, MD
Outcome results
None listed