Adaptive phase II randomized non-comparative trial of nivolumab after induction treatment in triple-negative breast cancer (TNBC) patients: TONIC-trial
- Conditions
- Breast cancertriple negative10006291
- Registration Number
- NL-OMON47543
- Lead Sponsor
- ederlands Kanker Instituut
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 84
- metastatic ER and HER2 negative breast cancer
- 18 years or older
- metastatic lesions accessible for histological biopsy
- maximum of three lines of chemotherapy for metastatic disease
- measurable or evaluable disease according to RECIST 1.1
- disease free interval (defined as time between first diagnosis or local
recurrence and first metastasis) longer than 1 year
- WHO performance status 0 or 1
- Subjects with brain metastases are eligible if these have been treated and
there is no magnetic resonance imaging (MRI) evidence of progression for at
least 4 weeks after treatment is completed and prior to first dose of study
drug administration. There must also be no requirement for immunosuppressive
doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at
least 2 weeks prior to study drug administration
- Signed written informed consent
- known leptomenigeal disease localization- history of having recceived 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 an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4
antibody
- current pregnancy or breastfeeding
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Progression-free survival (PFS1, time from randomization to tumor progression<br /><br>or death) Progression as defined by RECIST 1.1 will be used.<br /><br>• For the first stage of the trial, proportion of patients with PFS of at least<br /><br>12 weeks in each treatment arm. Treatment arms with >30% of patients with PFS<br /><br>of at least 12 weeks will continue to stage II of the study. Progression as<br /><br>defined by RECIST 1.1 will be used.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Progression-free survival (PFS1, time from randomization to tumor progression<br /><br>or death). Progression as defined by modified RECIST 1.1 for immune-based<br /><br>therapeutics (iRECIST) will be used<br /><br>Progression-free survival (PFS2, time from nivolumab treatment initiation to<br /><br>tumor progression) Progression as defined by RECIST 1.1 and iRECIST will be<br /><br>used.<br /><br>• Overall response rate ORR (complete response CR or partial response PR) at 12<br /><br>weeks, and at 6 months according to RECIST 1.1 and iRECIST will be used<br /><br>• Clinical benefit rate (CR+PR+stable disease >= 6 months and CR+PR+stable<br /><br>disease >= 3 months) according to RECIST 1.1 and iRECIST will be used<br /><br>• Overall survival (OS, time from start nivolumab to death from any cause)<br /><br>• Percentage of patients with toxicity (classified according to CTCAE v4.0 and<br /><br>immune-related toxicity</p><br>