An open-label, randomized, controlled, multicenter phase III study to assess the efficacy and safety of monotherapy with Olaparib versus physician's choice chemotherapy in the treatment of patients with metastatic breast cancer with BRCA1/2 germline mutations.
Summary description of the study
The aim of this study is to investigate whether a new treatment with a drug called Olaparib is effective in treating advanced breast cancer in patients with a BRCA1 or BRCA2 mutation compared to a chemotherapy chosen by the study physician (Capecitabine, Vinorelbine, or Eribulin). A mutation is a change in the genetic material, DNA, which can impact the course of certain processes in the body. BRCA stands for "Breast Cancer Susceptibility Gene," also referred to as the breast cancer gene in English. Individuals with a BRCA1 or BRCA2 mutation have an increased risk of developing cancer (primarily breast and ovarian cancer). Approximately 310 patients worldwide, including about 12-15 patients from Switzerland, will be randomly assigned in a 2:1 ratio to treatment with Olaparib or chemotherapy (Capecitabine, Vinorelbine, or Eribulin). The study duration varies for each participant. If the study medication is well tolerated, it will be taken until the cancer worsens.
(BASEC)
Intervention under investigation
The drug Olaparib inactivates an enzyme in the body called PARP (Poly ADP-ribose polymerase). The PARP enzyme helps normal cells repair damaged DNA. The drug Olaparib therefore prevents the damaged DNA from being repaired. However, normal cells still have other ways to repair DNA, allowing these normal cells to survive. Cancer cells without BRCA1 or BRCA2 cannot perform this repair when exposed to Olaparib. Therefore, these cancer cells die. This is why Olaparib is being tested in patients with a mutation of the BRCA1 or BRCA2 genes, as it is likely to be more effective in these patients.
Treatment Group 1: Olaparib
- oral 2 times daily 2 tablets (150 mg per tablet, total 600 mg daily)
Treatment Group 2: Physician's choice chemotherapy
- either Capecitabine 2500 mg/m2, oral tablets (in 2 doses) daily for 14 days, repetition every 3 weeks
- or Vinorelbine 30 mg/m2, intravenous on Day 1 and Day 8, repetition every 3 weeks
- or Eribulin 1.4 mg/m2, intravenous on Day 1 and Day 8, repetition every 3 weeks
(BASEC)
Disease under investigation
Patients with breast cancer and evidence of metastases who have a documented pathogenic mutation in the BRCA1/2 gene. Mutations in BRCA1 and BRCA2 are the most important causes of hereditary breast cancer.
(BASEC)
The main inclusion criteria are: - clinically confirmed breast cancer with evidence of metastases - germline mutation in the BRCA1/2 gene (if known) or eligible for BRCA mutation testing according to local guidelines - prior therapy with an anthracycline (e.g., Doxorubicin, Epirubicin) and a taxane (e.g., Paclitaxel or Docetaxel), either before or after surgery or as part of treatment for an advanced tumor - prior platinum-based chemotherapy (e.g., Cisplatin, Carboplatin) is allowed, provided there was no progression of the cancer under this treatment (BASEC)
Exclusion criteria
The main exclusion criteria are: - prior treatment with a PARP inhibitor - patients with HER2-positive disease - more than 2 prior lines of chemotherapy for metastatic breast cancer - untreated and/or uncontrolled brain metastases - prior cancer, unless successfully treated and the patient was disease-free for >5 years prior to entry into the study (BASEC)
Trial sites
Bern, Lausanne, Zurich
(BASEC)
Sponsor
AstraZeneca
(BASEC)
Contact
Contact Person Switzerland
Zürrer Marcela
+41(0)417257605
marcela.zuerrer@clutterastrazeneca.comAstraZeneca
(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
26.10.2015
(BASEC)
ICTRP Trial ID
not available
Official title (approved by ethics committee)
A randomised, double-blind, parallel group, placebo-controlled multi-centre Phase III study to assess the efficacy and safety of olaparib versus placebo as adjuvant treatment in patients with germline BRCA1/2 mutations and high risk HER2 negative primary breast cancer who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy (BASEC)
Academic title
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Public title
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Disease under investigation
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Intervention under investigation
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Type of trial
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Trial design
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Inclusion/Exclusion criteria
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Primary and secondary end points
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Registration date
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Incorporation of the first participant
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Secondary sponsors
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Additional contacts
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Secondary trial IDs
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Results-Individual Participant Data (IPD)
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Further information on the trial
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Results of the trial
Results summary
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Link to the results in the primary register
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