UNRESECTABLE MALIGNANT MESOTHELIOMA MedDRA version: 20.0 Level: PT Classification code 10027406 Term: Mesothelioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tremelimumab
Pharmaceutical Form: Solution for infusion
Product Name: MEDI4736
Pharmaceutical Form: Solution for infusion
Sponsors
FONDAZIONE NIBIT NETWORK ITALIANO PER LA BIOTERAPIA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ¿ Histologically or cytologically confirmed pleural or peritoneal malignant mesothelioma. ¿ Subjects who have refused a first line approved chemotherapy, or subjects in progression of disease after a maximum of one line of platinum-based therapy for advanced disease. ¿ Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment according to the modified RECIST for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma. ¿ Disease not amenable to curative surgery ¿ Age 18 and over at the time of consent ¿ ECOG Performance status of 0 or 1 ¿ Life expectancy > 12 weeks ¿ Negative screening test results for human immunodeficiency virus (HIV), hepatitis B and C. If positive results are not indicative of true active or chronic infection, the subjects can enter the study. ¿ Adequate bone marrow, hepatic and renal function determined within 14 days prior to start treatment ¿ Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: =60 years old and no menses for ¿1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. In addition, they must refrain from egg donation for 180 days after the final dose of investigational product. ¿ Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Days 1 through 180 post last dose. In addition, they must refrain from sperm donation for 180 days after the final dose of investigational product. ¿ Subject must be willing and able to provide written informed consent, and the trial have to be approved by the institutional review board at each institution. ¿ Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: ¿ Involvement in the planning and/or conduct of the study. ¿ Participation in another clinical study with an investigational product during the last 6 weeks ¿ Any previous treatment with a CTLA4, PD-1 or PD-L1 inhibitor, including tremelimumab or MEDI4736. ¿ History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease =3 years before the first dose of study drug and of low potential risk for recurrence; Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. ¿ Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) = 6 weeks prior to the first dose of study drug ¿ Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Bazett’s Correction ¿ Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid ¿ Any unresolved toxicity (CTCAE grade >2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy) ¿ Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 ¿ Active or prior documented autoimmune disease or inflammatory disorders (including inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis), diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegener syndrome) within the past 2 years NOTE: Subjects with vitiligo, alopecia Grave’s disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded. ¿ History of primary immunodeficiency ¿ History of allogeneic organ transplant ¿ History of hypersensitivity to MEDI4736 or tremelimumab or any excipient ¿ Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent ¿ Known history of previous clinical diagnosis of tuberculosis ¿ History of leptomeningeal carcinomatosis ¿ Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving tremelimumab and MEDI4736. ¿ Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids. ¿ Subjects with uncontrolled seizures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the immune-related (ir)-ORR (proportion of subjects with complete response [CR] or partial Response [PR]) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively.;Secondary Objective: 1) To estimate the ir-Disease Control Rate (DCR) (proportion of subjects with ir-CR, ir-PR, ir-stable disease) according to the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively; 2) To estimate the DCR according to the modified RECIST or RECIST 1.1 in pleural or peritoneal subjects, respectively; 3) To estimate the ir-progression free survival (PFS) according the ir-modified-RECIST or ir-RECIST 1.1 in pleural or peritoneal subjects, respectively; 4) To estimate the PFS according the modified-RECIST and RECIST 1.1 in pleural or peritoneal subjects, respectively; 5) To estimate the overall survival (OS) in treated subjects; 6) To estimate the ir-ORR, ir-DCR, ir-PFS, OS based on the PD-L1 status of tumor tissue 7) To assess safety and tolerability of the combination regimen according to NCICTCAE V. 4.0 in treated subjects;Primary end point(s): The primary endpoint is the objective response rate (ORR) is defined as the proportion of subjects with confirmed CR or PR based on ir-modified RECIST criteria for pleural mesothelioma and ir-RECIST criteria v 1.1 for peritoneal mesothelioma.;Timepoint(s) of evaluation of this end point: 60 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Ir-Disease control rate (DCR) is defined as the proportion of subjects with best response of ir-CR, ir-PR, or ir-SD, ; DCR is defined as the proportion of subjects with best response of CR, PR, or SD will be evaluated according to the modified RECIST criteria ; The ir-Progression-free-survival (ir-PFS) will be measured from the enrollment in the study to the documentation of confirmed disease progression based on the ir-modified RECIST criteria ; The PFS will be measured from the enrollment in the study to the documentation of disease progression according to the modified RECIST criteria for pleural mesothelioma and RECIST criteria v 1.1 for peritoneal mesothelioma, or death due to any cause, whichever occurs first; The OS is defined as the time from enrolment in the study until death due to any cause. ; 6) Ir-ORR, ir-DCR, ir-PFS, DCR, PFS, OS will be evaluated based on PD-L1 tumor tissue status.;Timepoint(s) of evaluation of this end point: 60 weeks; 60 weeks; 60 weeks; 60 weeks; 120 weeks; 120 weeks | — |
Countries
Italy
Contacts
Public ContactStudy Coordinator Studio NIBIT-MESO
Fondazione NIBIT
Outcome results
None listed