BEACON - Targeting the C1 Subtype of High Grade Serous Ovarian Cancer (BEACON)
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|ClinicalTrials.gov Identifier: NCT03363867|
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : September 26, 2018
Epithelial ovarian cancer (EOC) is the ninth most common cause of cancer in Australian women, with an estimated 1500 new diagnoses in Australia in 2015, and remains the seventh most common cause of cancer death in Australian women. High grade serous ovarian cancer (HGSC) is the most common form of Epithelial Ovarian Cancer, and accounts for the most deaths due to a gynaecological cancer.
The majority of women diagnosed with High Grade Serous Ovarian Cancer present with advanced disease, and are typically managed with a combination of cytoreductive surgery and platinum-based chemotherapy. Despite initial good response rates to chemotherapy, High Grade Serous Ovarian Cancer recurs in up to 70% of patients who present with Stage III/IV disease.
The molecular characteristics of High Grade Serous Ovarian Cancer have recently been extensively described in multiple studies. One of the consistent features identified are four distinct molecular subtypes that are based on gene expression profiles.These four subtypes are associated with differential clinical outcome that are largely consistent across multiple datasets. The subtypes may also be predictive for benefit from certain types of treatment.
The "C1" or mesenchymal subtype is pathologically characterised by an excessive fibrotic response of the stroma surrounding tumours, a process that is collectively referred to as desmoplasia. Patients with C1 High Grade Serous Ovarian Cancer have an increased incidence of primary treatment failure and poor overall survival (OS).
The purpose of this research project is to test how safe and effective the combination treatment of cobimetinib, bevacizumab and atezolizumab is as a treatment for patients with a C1 subtype of platinum resistant or refractory ovarian, fallopian tube or peritoneal cancer.
Cobimetinib is a drug that blocks a protein called Mitogen-activated protein kinase (MEK). MEK proteins are involved in the multiplication of cancer cells. By binding to the MEK protein, cobimetinib may help to stop the growth of your cancer cells.
Bevacizumab is an antibody (a type of protein produced by the immune system) that is specifically designed to block a protein called Vascular Endothelial Growth Factor (VEGF). VEGF is a protein that can increase the growth of tumour cells and binding to VEGF may help to stop the growth of tumours.
Atezolizumab is a type of drug called a Programmed Cell Death Protein 1 (PD-L1) inhibitor. PD-L1 binds to PD-1 which is a type of protein found on the surface of cells in your body's immune system, and it controls the ability of your body's natural immune response to trigger the death of tumour cells. Tumour cells can hide from the immune system by using PD-L1, which stops your immune system from triggering tumour cell death.
Atezolizumab is a drug designed to block this PD-1/PD-L1 interaction by binding to PD-L1 so that PD-1 cannot bind to it and stops it from turning off your immune cells. This helps your immune system to recognise and destroy tumour cells. In turn, this potentially can stop or reverse the growth of your cancer.
Cobimetinib, bevacizumab and atezolizumab have been used alone or in combination in the treatment of many other cancers. Each of them are individually licensed for the treatment of cancers such as advanced melanoma, non-small cell lung cancer, and bladder cancer in Australia. However, this treatment combination is experimental and is not approved to treat ovarian, fallopian tube or peritoneal cancers in any country.
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma||Drug: Atezolizumab Drug: Bevacizumab Drug: Cobimetinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||BEACON - A Phase II Study of Bevacizumab, Atezolizumab and Cobimetinib in Targeting the C1 Subtype of High Grade Serous Ovarian Cancer|
|Actual Study Start Date :||July 10, 2018|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||February 28, 2023|
|Experimental: Atezolizumab, Bevacizumab and Cobimetinib (ABC)||
840mg every 2 weeks (i.e. Day 1 and Day 15 of each 28 day cycle) via intravenous infusion from Cycle 2 onwards.
Other Name: Tecentriq
5mg/kg every 2 weeks (i.e. Day 1 and Day 15 of each 28 day cycle) via intravenous infusion.
Other Name: Avastin
60mg per day, every day for 21 days (i.e. Day 1 to Day 21 of each 28 day cycle)
Other Name: Cotellic
- Overall Response Rate as assessed by RECIST 1.1. [ Time Frame: Assessed at 24 weeks after commencing treatment. ]
- The frequency and severity of adverse events with the combination treatment as assessed by CTCAE v4.03. [ Time Frame: Through study completion, on average 12 months. ]
- Progression free survival as assessed by RECIST 1.1. [ Time Frame: Through study completion, on average 6 months. ]
- Best overall response rate as assessed by RECIST 1.1. [ Time Frame: Through study completion, on average 12 months. ]
- Immune related tumour response rate according to iRECIST. [ Time Frame: Through study completion, on average 6 months. ]
- Immune related disease control rate according to iRECIST. [ Time Frame: Assessed at 6 months after commencing treatment. ]
- Best overall response rate as assessed by GCIG CA-125 criteria. [ Time Frame: Through study completion, on average 12 months. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363867
|Contact: George Au-Yeung||+61 3 8559 email@example.com|
|Contact: Laura Gallettafirstname.lastname@example.org|
|Peter MacCallum Cancer Centre||Recruiting|
|Melbourne, Victoria, Australia, 3000|
|Contact: George Au-Yeung email@example.com|
|Contact: Danny Rischin firstname.lastname@example.org|
|Principal Investigator: George Au-Yeung|
|Principal Investigator:||George Au-Yeung||Peter MacCallum Cancer Centre, Australia|