Status and phase
Conditions
Treatments
About
This is a multicentric double-blind, placebo controlled, phase III trial. In this study, patients who underwent to a surgical resection of pleural mesothelioma and are without signs of macroscopic residual disease will be randomized 2:1 to receive atezolizumab or placebo. Patients will be treated for 12 months or until recurrence, unacceptable toxicity or patient/physician decision, whichever occurs first.
Randomization will be done via a centralized system and patients will be stratified histology (epithelioid vs non epithelioid) and stage (I vs
>I). Patients will be radiologically evaluated after surgical procedure before starting therapy and then every 12 weeks for 24 months or until disease progression. At screening patients should be without macroscopic residual disease. Quality of life questionnaire will be administered to patient at baseline and every 12 weeks. During the study baseline tumor blocks will be centrally analyzed to determinate biological characteristics and gene expression.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria
Signed informed Consent Form
Age ≥ 18 years on day of signing informed consent
Histologically confirmed malignant pleural mesothelioma
Surgical resection (P/D), without macroscopic residual. For stage I patient without visceral involvement a total pleurectomy is allowed
Absence of measurable or non-measurable disease assessed with CT scan after surgery
Patients must have received at least no 4 cycles of platinum/pemetrexed
perioperative chemotherapy as per local practice (neoadjuvant or adjuvant or both). Less than 4 cycles of chemotherapy are allowed for clinical decisions
should occur within 50 days from surgical resection.
within 30 ±7 days from last dose of adjuvant treatment.
Performance status of 0-1 on the ECOG Performance Scale
Availability of a representative tumor specimen for exploratory biomarker research (see Section 4.5.6 for information on tumor specimens) A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study enrollment.
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: ANC ³ 1.5 ´ 109/L (1500/mL) without granulocyte colony-stimulating factor support Lymphocyte count ³ 0.5 ´ 109/L (500/mL) Platelet count ³ 100 ´ 109/L (100,000/mL) without transfusion Hemoglobin 9 g/dL Patients may be transfused to meet this criterion. AST, ALT, and alkaline phosphatase (ALP) £ 2.5 ´ upper limit of normal (ULN)
Bilirubin £ 1.5 ´ ULN with the following exception:
Patients with known Gilbert disease: bilirubin level £ 3 ´ ULN. Creatinine £ 1.5 ´ ULN Albumin ³ 25 g/L (2.5 g/dL) For patients not receiving therapeutic anticoagulation: INR or aPTT £ 1.5 ´ ULN
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Women must refrain from donating eggs during this same period.
A woman is considered to be of childbearing potential if she is postmenarcheal, hasnot reached a postmenopausal state (³12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andn withdrawal are not acceptable methods of contraception. If required per local guidelines or regulations, locally recognized acceptable methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
Women with a positive pregnancy test at enrollment or prior to administration of study medication will be excluded.
Exclusion Criteria
Patient with macroscopic residual disease after surgery, evaluated with CT scan
after surgery or adjuvant therapy
Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
Active infection requiring systemic therapy
Patient with positive result to Human Immunodeficiency Virus (HIV) (HIV 1/2
antibodies) test
Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) 7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. NOTE:
History of radiation pneumonitis in the radiation field (fibrosis) is permitted
Known active tuberculosis
Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable
angina
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of
study treatment, or anticipation of need for a major surgical procedure during the
study
Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia
Prior allogeneic stem cell or solid organ transplantation
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab15. Current treatment with anti-viral therapy for HBV
Treatment with investigational therapy within 28 days prior to initiation of study
treatment
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
Primary purpose
Allocation
Interventional model
Masking
162 participants in 2 patient groups, including a placebo group
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Central trial contact
Carmine Pinto, MD; Erika Gervasi, BS
Data sourced from clinicaltrials.gov
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