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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03363867




Registration number
NCT03363867
Ethics application status
Date submitted
28/11/2017
Date registered
6/12/2017
Date last updated
20/12/2019

Titles & IDs
Public title
BEACON - ABC in Recurrent Platinum Resistant HGSOC
Scientific title
BEACON - A Phase II Study of Bevacizumab, Atezolizumab and Cobimetinib in Patients With Recurrent Platinum Resistant High Grade Serous Ovarian Cancer
Secondary ID [1] 0 0
BEACON
Universal Trial Number (UTN)
Trial acronym
BEACON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Fallopian Tube Cancer 0 0
Primary Peritoneal Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Cobimetinib

Experimental: Atezolizumab, Bevacizumab and Cobimetinib (ABC) -


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

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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate as assessed by RECIST 1.1.
Timepoint [1] 0 0
Assessed at 24 weeks after commencing treatment.
Secondary outcome [1] 0 0
The frequency and severity of adverse events with the combination treatment as assessed by CTCAE v4.03.
Timepoint [1] 0 0
Through study completion, on average 12 months.
Secondary outcome [2] 0 0
Progression free survival as assessed by RECIST 1.1.
Timepoint [2] 0 0
Through study completion, on average 6 months.
Secondary outcome [3] 0 0
Best overall response rate as assessed by RECIST 1.1.
Timepoint [3] 0 0
Through study completion, on average 12 months.
Secondary outcome [4] 0 0
Immune related tumour response rate according to iRECIST.
Timepoint [4] 0 0
Through study completion, on average 6 months.
Secondary outcome [5] 0 0
Immune related disease control rate according to iRECIST.
Timepoint [5] 0 0
Assessed at 6 months after commencing treatment.
Secondary outcome [6] 0 0
Best overall response rate as assessed by GCIG CA-125 criteria.
Timepoint [6] 0 0
Through study completion, on average 12 months.

Eligibility
Key inclusion criteria
- 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:

1. Other histologies including clear cell, mucinous and carcinosarcomas are
excluded.

2. 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

1. WBC = 2.5 x 109/L

2. Hb = 9 gm/dl

3. ANC =1.5 x 109/L

4. Platelet count = 100 x 109/L

5. Creatinine clearance = 30mL/min (via Cockcroft-Gault)

6. Albumin =2.5 g/dL

7. Serum bilirubin = 1.5 the upper limit of normal (ULN); patients with known
Gilbert's disease may have a bilirubin = 3.0 x ULN

8. INR and PTT = 1.5 x ULN; amylase and lipase =1.5x ULN

9. AST, ALT, and alkaline phosphatase (ALP) =3 x ULN

- Absence of clinically significant proteinuria as demonstrated by urine dipstick = 1+
or < 1.0g of protein in a 24-hour urine collection

- Patients with =2+ protein on dipstick analysis at baseline must undergo a 24-hour
urine collection for protein and will remain eligible if <1.0g of protein is detected
within 2 weeks of randomisation

- Negative test results for Viral Hepatitis:

- Negative hepatitis B surface antigen (HBsAg) test at screening

- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screenin.The HBV
DNA test will be performed only for patients who have a positive total HBcAb test.

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening.The HCV RNA test will be
performed only for patients who have a positive HCV antibody test.

- Female participants must be postmenopausal (= 12 months of non-therapy-induced
amenorrhoea) or surgically sterile (absence of ovaries and/or uterus, or who received
therapeutic radiation to the pelvis) or otherwise have a negative serum pregnancy test
within 14 days of the first study treatment and agree to abstain from heterosexual
intercourse or use two effective contraceptive methods that result in a failure rate
of <1% per year during the whole treatment period of the study and for at least 3
months (if the last study dose contained cobimetinib), 5 months (if the last study
dose contained atezolizumab) or 6 months (if the last study dose contained
bevacizumab) after the last dose of study treatment. Women must refrain from donating
eggs during this same period.

- Patients must have recovered to = grade 1 from their treatment-related AE with the
exception of alopecia.

- Has consented to the use of their collected fresh tumour biopsies, archival FFPE
specimen, ascites and peripheral blood samples as detailed in the protocol for
translational research, including but not limited to DNA, RNA and protein based
biomarker detection.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- History of autoimmune disease including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis

- Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4
weeks prior to registration or at any time during the study and for at least 5 months
after the last dose of study drug.

- Active infection requiring IV antibiotics at screening

- Patients with known HIV infection or a history of positive tests for HIV/AIDS

- Current or recent (within 10 days of registration) use of acetylsalicylic acid (> 325
mg/day), clopidogrel (>75 mg/day) or thrombolytic agents for therapeutic purposes

- Patient has taken the following foods/supplements within 7 days prior to registration:
St John's wort or hyperforin (potent CYP3A4 enzyme inducer) or Grapefruit juice
(potent CYP3A4 enzyme inhibitor)

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any components of cobimetinib, atezolizumab, or bevacizumab
formulations

- History of clinically significant cardiac or pulmonary dysfunction including the
following; Inadequately controlled hypertension (that is defined as systolic blood
pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg that is treated or
untreated) or History of myocardial infarction within 6 months prior to first dose of
study drug in Cycle 1

- Prior history of hypertensive crisis or hypertensive encephalopathy

- Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent
arterial thrombosis) within 6 months of registration

- History of stroke or transient ischemic attack within 6 months prior of registration

- Patient has has a serious non-healing wound, active ulcer or untreated bone fracture

- History of hemoptysis (>½ teaspoon of bright red blood per episode), or any other
serious haemorrhage or at risk of bleeding (gastrointestinal history of bleeds,
gastrointestinal ulcers, etc.)

- History or evidence of inherited bleeding diathesis or significant coagulopathy at
risk of bleeding

- Any previous venous thromboembolism = Grade 3

- Left ventricular ejection fraction below institutional lower limit of normal

- Uncontrolled serious medical or psychiatric illness

- Uncontrolled tumour pain

- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan

- History or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment/central serous
chorioretinopathy, retinal vein occlusion or neovascular macular degeneration.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03363867
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
George Au-Yeung
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
George Au-Yeung
Address 0 0
Country 0 0
Phone 0 0
+61 3 8559 6507
Fax 0 0
Email 0 0
george.au-yeung@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03363867