Malignant Mesothelioma
Conditions
Keywords
Tremelimumab, anti-CTLA-4 monoclonal antibody, malignant mesothelioma
Brief summary
RATIONAL: Preliminary results fron the Study MESOT-TREM-2012 indicate a promising activity of tremelimumab in malignant mesothelioma (MM) patients. PURPOSE: The proposed study MESOT-TREM-2012 aims to explore the efficacy of a more intensive schedule of treatment with tremelimumab in 29 MM patients. Subjects will receive investigational product every 4 weeks (wks) for 6 doses, followed by doses every 12 wks until confirmed disease progression.
Detailed description
Primary endpoint: 1\) To assess the rate of objective clinical complete response (CR) or partial response (PR) Secondary endpoints: 1. To define toxicity profile according to NCI CT-CAE V. 3 2. To assess the overall survival (OS) 3. To estimate disease control rate (DCR) (proportion of patients with best response of CR+PR+SD) according to the modified Recist criteria 4. To assess the progression-free survival in treated patients according to modified Recist criteria 5. To evaluate qualitative and quantitative changes in cellular and humoral immune responses
Interventions
DRUGTremelimumab
Tremelimumab is administered as endovenous infusion
Sponsors
MedImmune LLC
Azienda Ospedaliera Universitaria Senese
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed MM * Have received only one prior systemic chemotherapy platinum-based regimen for advanced MM * Measurable disease, defined at least 1 unidimensionally measurable lesion \> 20 mm by conventional techniques or \> 10 mm by spiral CT scan (modified RECIST criteria) * Disease not amenable to curative surgery * No known brain metastasis * Age 18 and over * Performance status 0-2 * Life expectancy \> 12 weeks * Adequate hematologic, hepatic and renal function * Platelet count \> 75000/mm3 * Absolute granulocyte count \> 1000/mm3 * Hemoglobin \> 9 g/dL * Bilirubin total \< 1.5 x ULN (Upper limited normal), except patients with documented Gilbert's syndrome, who must have a total bilirubin \< 3.0 mg/dl * AST and ALT \< 2.5 x ULN ( \< 5 x ULN if documented liver metastasis are present) * Creatinine level \< 2mg/dl or calculated creatinine clearance \> 60 mL/min as determined by the Cockcroft Gault equation. * Not pregnant or nursing * Fertile patients must use effective contraception * Patient 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
Exclusion criteria
* Symptomatic chronic inflammatory or autoimmune disease * Active hepatitis B or C * Prior treatment with tremelimumab or other anti-CTLA-4 antibody or anti-PD1, anti-PDL-1 agents * Clinically relevant cardiovascular disease * History of psychiatric disabilities, potentially interfering with the capability of giving adequate informed consent * Uncontrolled active infections * Other concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents * History of other malignancies except for adequately treated basal cell carcinoma or squamous cell skin cancer or carcinoma of cervix, unless the patient has been disease-free for at least 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the objective response | Weeks 24 | The objective response is defined as a confirmed complete response (CR), or partial response (PR) according to the modified RECIST Criteria for pleural mesothelioma and the immune-related (ir) Response Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | 1 year | DCR is the proportion of treated subjects that achieved confirmed CR or PR or stable disease (SD) The DCR is assessed using the modified RECIST Criteria for pleural mesothelioma umor assessment and the the immune-related response criteria |
| Safety | 3 years | The assessment of safety includes serious and non-serious adverse events according to NCI-CTC criteria version 3.0. In addition, laboratory evaluation, abnormal vital signs and physycal examination findings are also included. |
| Progression free survival | 1 years | Progression free survival is computed from the first day of study treatment to the day of documented progression according to the modified RECIST Criteria for pleural mesothelioma or death, whichever occurs first |
Countries
Italy
Contacts
Primary ContactMichele Maio, MD
Backup ContactLuana Calabrò, MD
Outcome results
None listed