The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma
Malignant Mesothelioma
Conditions: official terms
Lung Neoplasms - Mesothelioma
Conditions: Keywords
Tremelimumab, anti-CTLA-4 monoclonal antibody, malignant mesothelioma
Study Type
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Tremelimumab
Type: Drug
Overall Status
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
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Siena, Italy
Status: Recruiting
Contact: Michele Maio, MD - +39-0577586335 -
Start Date
July 2012
Completion Date
January 2015
Azienda Ospedaliera Universitaria Senese
Azienda Ospedaliera Universitaria Senese
Record processing date processed this data on July 28, 2015 page