breast cancer MedDRA version: 20.0 Level: LLT Classification code 10024745 Term: Lobular breast carcinoma invasive System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Carboplatin
Pharmaceutical Form:
INN or Proposed INN: Carboplatin
CAS Number: 41575-94-4
Other descriptive name: CARBOPLATIN
Sponsors
NKI-AVL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed and written informed consent • Age 18 year or older • Metastatic or incurable locally advanced lobular breast cancer with confirmation of the lobular histology and E-cadherin loss or aberrant staining (IHC) on a biopsy of a metastatic lesion. For patients with a tumor with a mixed-type IDC/ILC or IDC with lobular features a loss or aberrant expression of E-cadherin (IHC) is required • Estrogen receptor expression of at least 10% on a metastatic lesion (independent of progesterone receptor expression and HER2 expression) • Metastatic lesion accessible for histological biopsies (Mandatory biopsies: pre-induction treatment with carboplatin, before start atezolizumab, after 2 cycles of atezolizumab. Optional: upon development of acquired resistance). Biopsies from bone lesions are not permitted. Interval between last chemotherapy and pre-induction biopsy has to be at least 14 days (not for endocrine treatment in view of the relatively long half-life). The pre-induction treatment biopsy has to contain sufficient tumor content (=100 tumor cells); subjects with samples that have insufficient tumor content will require re-biopsy prior to start carboplatin. • Evidence of progression of disease (either radiological or clinical) • Disease progression had to occur after previous endocrine (not necessarily the most recent) therapy in the advanced setting. Patients with an ER-positive tumor must have received an anti-estrogen (tamoxifen and/or fulvestrant) and at least one aromatase inhibitor for early breast cancer or metastatic disease. • A maximum of two lines of palliative chemotherapy for metastatic or incurable locally advanced breast cancer is allowed. HER2-targeting therapy is allowed for the HER2-positive cases. • WHO performance status of 0 or 1 • Evaluable disease or measurable according to RECIST 1.1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: • known 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 mg/day prednisone or equivalent) or chronic infections. Subjects with vitiligo, diabetes mellitus type I, psoriasis not requiring systemic treatment or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement, Sjøgren’s syndrome or conditions not expected to recur in the absence of an external trigger will not be excluded from the study. Adrenal replacement doses >10 mg/day prednisone or equivalent are permitted in the absence of active autoimmune disease • prior treatment with immune checkpoint blockade such as but not limited to anti-PD(L)1, anti-PD-L2, anti-CTLA-4, anti-GITR or CD137/OX40-agonist • live vaccine within 2 weeks prior to start of study, at any time during the study, or within 5 months following the last dose of atezolizumab. Inactivated vaccines are allowed • active other cancer • active hepatitis B (defined as having a positive hepatitis B surface antigen [HbsAg] test at screening) or active hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNActive tuberculosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: at 6 months;Main Objective: To assess the efficacy of atezolizumab in combination with carboplatin in metastatic ILC ;Primary end point(s): Proportion of patients who remain free of progression (time from start carboplatin to tumor progression or death from any cause) at 6 months. Progression as defined by RECIST 1.1 will be used.; Secondary Objective: • To evaluate the outcome after atezolizumab together with carboplatin in the IR-profile subgroup vs the non-IR-subgroup as defined by gene expression profiling(retrospectively defined as previously described [9]) • To evaluate the safety of atezolizumab together with carboplatin • To evaluate the efficacy of atezolizumab plus carboplatin using objective response rate • To evaluate the efficacy of atezolizumab plus carboplatin using proportion of patients free of progression at 12 months • To evaluate the efficacy of atezolizumab plus carboplatin using overall survival • To explore the role of potential biomarkers to predict response to atezolizumab plus carboplatin | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Proportion of patients free of progression (RECIST 1.1) at 6 months in the IR-profile subgroup vs the non-IR-subgroup as defined by gene expression profiling (retrospectively defined as previously described) 2) Progression as defined by iRECIST 3) Percentage of patients with toxicity (according to CTCAE v4.0.3, Appendix A) and immune-related toxicity defined as the Adverse Events of Special Interest (AESI's) for atezolizumab 4) Objective response rate (RECIST 1.1) 5) Proportion of patients who remain free of progression at 12 months. Progression as defined by RECIST 1.1 will be used. 6) Overall survival ;Timepoint(s) of evaluation of this end point: At 6 months (1), at end of treatment (2, 3, 4), at 12 months (5), at death (6) | — |
Countries
Netherlands
Contacts
Public ContactDr. M. Kok
NKI-AVL
Outcome results
None listed