Biomarker discovery randomized phase IIb trial with carboplatin-cyclophosphamide versus paclitaxel with or without Bevacizumab as first-line treatment in advanced triple negative Breast cancer (TRIPLE-B study);Title after protocol amendment August 12, 2017: Biomarker discovery randomized phase IIb trial with carboplatin-cyclophosphamide versus paclitaxel with or without atezolizumaB as first-line treatment in advanced triple negative Breast cancer (TRIPLE-B study)

Phase 2

Recruiting

Conditions: breast cancer
triple negative breast cancer
10006291

Registration Number: NL-OMON52986

Lead Sponsor: BOOG Study Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 304

Inclusion Criteria

- Histologically confirmed triple negative metastasized or locally advanced
incurable breast cancer. See protocol section 5.2 for more details.
- Histological confirmation of triple negative breast cancer of a metastatic
lesion is
recommended
- Histological or cytological confirmation of metastatic breast cancer is
required in case of
normal CA 15.3 levels. Exception: see protocol section 5.2 for details.
- Primary tumor or metastasis tissue sent to NKI-AVL for BRCA-like testing
- Pretreatment histological biopsy of a metastatic lesion for the
translational research
questions (tumor tissue from bone metastases cannot be used). Exception: see
protocol section 5.2 for details.
- No previous cytotoxic therapy for metastatic disease
- Disease-free interval of at least 12 months after completion of (meo)adjuvant
paclitaxel or (neo)adjuvant platinum compound
- Disease-free interval of at least 6 months after completion of (neo)adjuvant
docetaxel
- Measurable or evaluable disease according to RECIST v1.1
- WHO performance status of 0 or 1

Exclusion Criteria

- Receptor conversion to hormone receptor positive (defined as >= 10% ER
positive tumor cells) or HER2 positive
- Other antitumor therapy within the previous 21 days with the exception of
recently started (within 21 days of randomization) endocrine therapy.
- Radiotherapy with palliative intent within the previous 7 days before start
study medication (see protocol 5.3 for details)
- Known CNS disease except for treated brain metastases (see protocol 5.3 for
details)
- Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03) at
inclusion)
- Use of denosumab is not allowed. See protocol section 5.3 for details.
- Severe infection in the last 4 weeks.
- Antibiotics in the last 2 weeks.
- History of autoimmune disease. See protocol section 5.3 for details.
- Prior allogeneic stem cell or solid organ transplantation
- History of lung diseases such as idiopathic pulmonary fibrosis, pneumonitis.
See protocol section 5.3 for more details
- An infection requiring parenteral antibiotic
- Positive test for hepatitis B, C HIV. See protocol section 5.3 for more
details.
- Active tuberculosis.
- Live, attenuated vaccine within 4 weeks prior to randomization.
- Prior treatment with anti cancer vaccins or immune checkpoint blockade
therapies, including anti-CTLA-4, CD137 agonist, OX40 agonist, anti-PD-1, or
anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents, systemic corticosteroids or
other systemic immunosuppressive medications. See protocol section 5.3 for
details.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Modified primary variable after implementation of protocol amendment February<br /><br>2017: Primary Outcome Measures (2x2 factorial design): Interaction test of<br /><br>BRCA-like status vs. treatment (CC vs. Paclitaxel (both arms with or without<br /><br>atezolizumab).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Modified secundary variable after implementation of protocol amendment February<br /><br>2017: Secondary Outcome Measures: • PFS benefit of the addition of<br /><br>atezolizumab. • PD-L1 status and PFS • CD8 + TIL abundance and PFS • Moleculair<br /><br>subtypes and PFS • Predictive biomarkers for PFS gain. • PFS of the two first<br /><br>line chemotherapeutic regimens, regardless of bevacizumab yes or no. • Overall<br /><br>survival. • Adverse events.</p><br>