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BEAT-meso: Bevacizumab and Atezolizumab in Malignant Pleural Mesothelioma (BEAT-meso)

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ClinicalTrials.gov Identifier: NCT03762018
Recruitment Status : Recruiting
First Posted : December 3, 2018
Last Update Posted : October 10, 2019
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Tracking Information
First Submitted Date  ICMJE November 20, 2018
First Posted Date  ICMJE December 3, 2018
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE April 30, 2019
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Progression-free Survival (PFS) according to the mRECIST v1.1 [ Time Frame: From date of randomisation until documented progression or death, if progression is not documented, assessed up to 67 months ]
    A co-primary endpoint, defined as the time from the date of randomisation until documented progression (according to the mRECIST v1.1) or death, if progression is not documented. Censoring (for participants without a PFS/death event) will occur at the last tumour assessment if the patient is lost to follow-up or refuses further documentation of follow-up.
  • Overall Survival (OS) [ Time Frame: From date of randomisation until death from any cause, assessed up to 67 months ]
    The second co-primary endpoint, overall survival, is defined as the time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03762018 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Overall Response (OR) [ Time Frame: From start of protocol treatment accorss all time-points until end of protocol treatment, assessed up to 67 months ]
    Defined as the best overall response [complete response (CR) or partial response (PR)] evaluated according to the mRECIST v1.1
  • Disease Control (DC) at 24 weeks [ Time Frame: 24 weeks after protocol treatment start ]
    Defined as complete or partial response, or disease stabilisation at 24 weeks.
  • Time to Treatment Failure (TTF) [ Time Frame: From randomisation until discontinuation of protocol treatment for any reason, assessed up to 67 months ]
    Defined as the time from the date of randomisation to discontinuation of protocol treatment for any reason (including progression of disease, treatment toxicity, refusal and death). Censoring will occur at the last follow-up date.
  • Duration of Response (DoR) [ Time Frame: From date of first documentation of objective response until date of first documented progression or relapse, assessed up to 67 months ]
    Defined as the interval from the date of first documentation of objective response (complete response or partial response, according to the mRECIST v1.1) to the date of first documented progression or relapse.
  • Number of participants with treatment related adverse events according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: Assessed from the date of informed consent until 90 days after protocol treatment discontinuation. Analysed at 67 months after randomisation of the first patient ]
    Assessed through analysis of the worst grade of toxicity/adverse events and will include all participants who received at least one dose of protocol treatment. Adverse events leading to dose interruption, withdrawal of protocol treatment and deaths, laboratory parameters and abnormalities and vital signs over the whole treatment period will be assessed and graded according to CTCAE v5.0 criteria.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BEAT-meso: Bevacizumab and Atezolizumab in Malignant Pleural Mesothelioma
Official Title  ICMJE A Multicentre Randomised Phase III Trial Comparing Atezolizumab Plus Bevacizumab and Standard Chemotherapy Versus Bevacizumab and Standard Chemotherapy as First-line Treatment for Advanced Malignant Pleural Mesothelioma
Brief Summary The aim of this clinical trial is to assess the effect of treatment with a monoclonal antibody called atezolizumab in patients diagnosed with a type of lung cancer called malignant pleural mesothelioma. The efficacy (whether the treatment works), safety and tolerability (side effects of treatment) of atezolizumab plus bevacizumab in combination with standard chemotherapy versus bevacizumab in combination with standard chemotherapy will be investigated.
Detailed Description

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer arising from the mesothelial surface of the pleura. In Europe, the incidence is about 20 per million and is almost always caused by asbestos exposure, with a usual lag time of 30 years between exposure and presentation. Patients diagnosed with advanced MPM have limited treatment options, representing a strict unmet need. Despite decades of clinical research, cytotoxic chemotherapy remains one of the few therapeutic options that has been proven to improve survival in advanced MPM in a randomised controlled trial.

The combination of cisplatin and pemetrexed has become standard first-line therapy worldwide for patients who are not suitable for aggressive surgery or in whom chemotherapy is recommended as part of a multimodality regimen. Carboplatin is often substituted for cisplatin, due to simpler and shorter administration and assumption of a more favourable toxicity profile based on experience in other diseases. Patients with MPM have limited treatment options, representing a strict unmet need.

An antibody is a common type of protein usually made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. The two monoclonal antibodies (atezolizumab and bevacizumab) used in this trial are laboratory-produced antibodies. Atezolizumab is engineered to attach to immune cells to stimulate their activity against cancer cells.

Atezolizumab and bevacizumab are both approved by the European Medicines Agency for the treatment of lung and other cancers. The addition of atezolizumab to bevacizumab plus standard chemotherapy for the treatment of MPM is being investigated in this trial.

All participants will receive 4-6 cycles of standard chemotherapy consisting of carboplatin AUC 5 (area under the plasma concentration versus time curve) plus pemetrexed 500mg/m^2 given intravenously, on day 1 of every 3 week cycle for about 12 to 18 weeks.

Participants will be randomly assigned to one of two treatment groups:

Treatment 1

  • Bevacizumab 15 mg/kg intravenously on day 1 of every 3-week cycle, plus
  • 4-6 cycles of chemotherapy

OR

Treatment 2

  • Atezolizumab 1200 mg fixed dose intravenously on day 1 of every 3-week cycle, plus
  • Bevacizumab 15 mg/kg, intravenously on day 1 of every 3-week cycle, plus
  • 4-6 cycles of chemotherapy

Participants will continue to receive treatment until disease progression, or until treatment is stopped at the request of the participant or treating doctor, or the participant withdraws consent.

A total of 320 participants from approximately 45 centres in Europe are expected to be included in this trial which will take approximately 6 years to be completed after the first participant is enrolled.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pleural Mesothelioma Malignant Advanced
Intervention  ICMJE
  • Drug: Carboplatin
    Carboplatin belongs to the group of medicines known as alkylating agents. Carboplatin interferes with the growth of cancer cells, which eventually are destroyed.
    Other Name: Carboplatin Accord
  • Drug: Pemetrexed
    Pemetrexed is a type of drug known as an anti metabolite. It stops cells making and repairing DNA so they can't grow and multiply.
    Other Name: Alimta
  • Drug: Bevacizumab
    Bevacizumab is an angiogenesis inhibitor. It works by targeting a protein called vascular endothelial growth factor (VEGF) that helps cancers form new blood vessels. By stopping this process, bevacizumab 'suffocates' the blood supply to the cancer, shrinking it and stopping it from growing.
    Other Name: Avastin
  • Drug: Atezolizumab
    Atezolizumab is in a class of medications called monoclonal antibodies. It works by blocking the action of a certain protein in cancer cells. This helps the immune system to fight against the cancer cells, and helps to slow tumor growth.
    Other Names:
    • Tecentriq
    • RO5541267
Study Arms  ICMJE
  • Active Comparator: Bevacizumab plus chemotherapy
    Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
    Interventions:
    • Drug: Carboplatin
    • Drug: Pemetrexed
    • Drug: Bevacizumab
  • Experimental: Atezolizumab plus bevacizumab plus chemotherapy
    Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m^2 intravenously on day 1 every 3 weeks
    Interventions:
    • Drug: Carboplatin
    • Drug: Pemetrexed
    • Drug: Bevacizumab
    • Drug: Atezolizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 30, 2018)
320
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed advanced malignant pleural mesothelioma (all histological subtypes are eligible)
  • Not amenable for radical surgery based on local standards
  • Evaluable disease or measurable disease as assessed according to the modified response evaluation criteria for solid tumours for mesothelioma (mRECIST) v1.1
  • Availability of tumour tissue for translational research
  • Age >18 years
  • Performance Status 0-1
  • Life expectancy >3 months
  • Adequate haematological, renal and liver function
  • Completed baseline quality of life (QoL) questionnaire
  • Women of childbearing potential and sexually active men must agree to use highly effective contraception
  • Able to understand and give written informed consent and comply with trial procedures

Exclusion Criteria:

  • Prior treatment for malignant pleural mesothelioma
  • Treatment with systemic immune-stimulatory agents within 4 weeks or five half-lives of the drug prior to randomisation and during protocol treatment.
  • Treatment with systemic immunosuppressive medications within 2 weeks prior to randomisation and during protocol treatment.
  • Previous allogeneic tissue/solid organ transplant
  • Live vaccines within 4 weeks prior to first dose of protocol treatment
  • Inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease within 6 months prior to randomisation
  • History of haemoptysis
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Barbara Ruepp, PharmD +41 31 511 94 00 barbara.ruepp@ibcsg.org
Contact: Florence Berger, PhD +41 31 511 94 48 BEAT-meso@etop-eu.org
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Portugal,   Slovenia,   Spain,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03762018
Other Study ID Numbers  ICMJE ETOP 13-18
2018-002180-25 ( EudraCT Number )
MO40388 ( Other Identifier: F.Hoffman-La Roche Ltd )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party European Thoracic Oncology Platform
Study Sponsor  ICMJE European Thoracic Oncology Platform
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Study Chair: Enriqueta Felip, MD-PhD Vall d'Hebron University Hospital
Study Chair: Sanjay Popat, PhD, MBBS Royal Marsden NHS Foundation Trust
PRS Account European Thoracic Oncology Platform
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP