BEACON - ABC in Recurrent Platinum Resistant HGSOC

NCT03363867 | Unknown Phase 2

• 1 other identifier: BEACON
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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 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 platinum resistant or refractory high grade serous 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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Keywords

High grade serous; Platinum resistant; Recurrent ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate as assessed by RECIST 1.1.

  Assessed at 24 weeks after commencing treatment.

Secondary Outcomes (6)

• The frequency and severity of adverse events with the combination treatment as assessed by CTCAE v4.03.

  Through study completion, on average 12 months.

• Progression free survival as assessed by RECIST 1.1.

  Through study completion, on average 6 months.

• Best overall response rate as assessed by RECIST 1.1.

  Through study completion, on average 12 months.

• Immune related tumour response rate according to iRECIST.

  Through study completion, on average 6 months.

• Immune related disease control rate according to iRECIST.

  Assessed at 6 months after commencing treatment.

Study Arms (1)

Atezolizumab, Bevacizumab and Cobimetinib (ABC)

EXPERIMENTAL

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Cobimetinib

Interventions

Atezolizumab DRUG

840mg every 2 weeks (i.e. Day 1 and Day 15 of each 28 day cycle) via intravenous infusion from Cycle 2 onwards.

Also known as: Tecentriq

Atezolizumab, Bevacizumab and Cobimetinib (ABC)

Bevacizumab DRUG

5mg/kg every 2 weeks (i.e. Day 1 and Day 15 of each 28 day cycle) via intravenous infusion.

Also known as: Avastin

Atezolizumab, Bevacizumab and Cobimetinib (ABC)

Cobimetinib DRUG

60mg per day, every day for 21 days (i.e. Day 1 to Day 21 of each 28 day cycle)

Also known as: Cotellic

Atezolizumab, Bevacizumab and Cobimetinib (ABC)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female patients with high grade serous ovarian carcinoma.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent
• Able to comply with the study protocol and follow-up procedures, in the investigator's judgement
• Female patients aged ≥ 18 years at screening
• Patients with a histological diagnosis of invasive high grade serous ovarian carcinoma (HGSC) including fallopian tube and primary peritoneal cancers, as defined by histological diagnosis and immunohistochemistry profile consistent with high grade serous cancer:
• Other histologies including clear cell, mucinous and carcinosarcomas are excluded.
• Mixed histologies are allowed provided that \>80% of the primary tumour is high grade serous based on diagnostic pathology review and immunohistochemistry profile consistent with high grade serous (i.e. positive for WT1, PAX8 and P53)
• Platinum resistant or refractory recurrent disease defined by GCIG CA-125 criteria or RECIST v1.1 disease progression on or within 6 months of last platinum-based chemotherapy.
• Disease that is measurable according to RECIST 1.1 and amenable to biopsy (note that lesions intended to be biopsied should not be target lesions).
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Life expectancy greater than 3 months
• Adequate hematologic and organ function, defined by the following laboratory results obtained within 7 days prior to registration
• WBC ≥ 2.5 x 109/L
• Hb ≥ 9 gm/dl
• ANC ≥1.5 x 109/L
• Platelet count ≥ 100 x 109/L

You may not qualify if:

• Prior treatment with CD137 agonists or immune checkpoint blockage therapies, anti programmed death-1, anti-program death-ligand 1, MEK inhibitor. Prior treatment with bevacizumab is allowed, provided a \>6 month treatment free interval from the last previous dose of bevacizumab to registration.
• Treatment with systemic immunosuppressive medications, including but not limited to corticosteroids, cyclophosphamide, azathioprine, cyclosporine, methotrexate, thalidomide and anti-tumour necrosis factor (TNF) agents within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial
• Patient has had surgical procedures or significant traumatic injury within 60 days prior to registration, or it is anticipated that they will require major surgical procedures during the course of the study.
• Patients at high risk of bowel perforation or fistula
• History of bowel obstruction, including sub- occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess.
• History of colonic anastamosis
• Clinical symptoms of recent bowel obstruction or paralytic ileus, but excluding postoperative, or evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan.
• Prior treatment with Hyperthermic intraperitoneal chemotherapy (HIPEC)
• Prior whole abdominal or pelvic radiotherapy
• Untreated CNS metastases. Treatment of brain metastases, either by surgical or radiation techniques, must have been completed at least 4 weeks prior to registration. Prior to registration, there are no signs of progression or hemorrhage of treated CNS metastases, eg. by MRI Brain. No ongoing need for corticosteroid treatment (anticonvulsants are allowed)
• Treatment with any investigational agent or approved therapy within 28 days or two investigational agent half-lives (whichever is longer) prior to registration.
• Malignancies other than ovarian cancer within 5 years prior to registration (or within 3 years prior to registration, provided probability of recurrence is \<10%) with the exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, melanoma in situ, and ductal carcinoma in situ treated surgically with curative intent.
• Prior radiation therapy within 28 days prior to registration and/or persistence of radiation-related adverse effects.
• Spinal cord compression not definitively treated with surgery and/or radiation.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

atezolizumab; Bevacizumab; cobimetinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• George Au-Yeung

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 6, 2017
• Study Start: July 10, 2018
• Primary Completion: February 28, 2024
• Study Completion: June 30, 2025
• Last Updated: August 7, 2023

Record last verified: 2023-08

Locations

AU (1)