Malignant Mesothelioma
Conditions
Keywords
Tremelimumab, Malignant Mesothelioma, anti-CTLA-4 mAb
Brief summary
The study is designed to define the immunologic and clinical activity of Tremelimumab in patients with advanced mesothelioma.
Detailed description
No effective standard treatment can improve significantly the prognosis of malignant mesothelioma (MM) patients. However, there is evidence that MM patients may benefit from immunotherapeutic agents. Clinical studies examining CTLA-4 blockade are providing convincing evidences on the immunobiological effects and on the clinical activity of this new class of immunomodulating therapeutic agents, likely due to their ability to stimulate patients'immune system to more effectively attack tumor cells by blocking a negative regulatory signal. Tremelimumab is a fully human anti-CTLA-4 monoclonal antibody (mAb), developed as an IgG2 isotype to minimize complement activation and reduce the risk of cytokine storm. As a single agent, Tremelimumab can induce durable tumor regression in 7-10% of patients with advanced melanoma. Tremelimumab has been tested in several clinical trials as single-agent or in combination with other agents in different solid tumors. The evidences above unveil a strong immunologic potential of treatment with Tremelimumab also in MM patients.
Interventions
DRUGTremelimumab
Given IV
Sponsors
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 malignant mesothelioma (MM) * Have received only one prior systemic chemotherapy platinum-based regimen for advanced MM * 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 * Not pregnant or nursing * 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 * Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or not compensated chronic heart disease in NYHA class II or more * 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 |
|---|---|---|
| Objective tumor response by modified Response Evaluation Criteria in Solid Tumor (RECIST) | Weeks 24 | The objective tumor response is defined as a confirmed complete response (CR) or partial response (PR) according to the modified RECIST criteria for pleural mesothelioma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate | 1 year | Disease control rate (DCR) is the proportion of treated subjects that achieved confirmed complete response, or partial response, or stable disease. The DCR is assessed using the modified RECIST criteria for pleural mesothelioma |
| Progression free survival | 1 year | 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 |
| Safety | 2 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 physical examination findings are also included. |
Countries
Italy
Outcome results
None listed