The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma

Malignant Mesothelioma Clinical Trial

Official title:

A SECOND-LINE, SINGLE ARM, PHASE II CLINICAL STUDY WITH TREMELIMUMAB, A FULLY HUMAN ANTI-CTLA-4 MONOCLONAL ANTIBODY, AS MONOTHERAPY IN PATIENTS WITH UNRESECTABLE MALIGNANT MESOTHELIOMA. The MESOT-TREM-2012

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01655888
• Other study ID #: MESOT-TREM-2012
• Secondary ID: 2012-002762-12
• Status: Recruiting
• Phase: Phase 2
• First received: July 31, 2012
• Last updated: July 31, 2012
• Start date: July 2012
• Est. completion date: January 2015

Study information

• Verified date: July 2012
• Source: Azienda Ospedaliera Universitaria Senese
• Contact: Michele Maio, MD
• Phone: +39-0577586335
• Email: mmaio[@]cro.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: January 2015
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Malignant Mesothelioma
• Mesothelioma

Intervention

Drug:
• Tremelimumab
Tremelimumab is administered as endovenous infusion

Locations

Country	Name	City	State
Italy	Medical Oncology and Immunotherapy Unit, University Hospital of Siena	Siena

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria Senese	MedImmune LLC

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the objective response	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	Weeks 24	No
Secondary	Disease control rate (DCR)	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	1 year	No
Secondary	Safety	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.	3 years	Yes
Secondary	Progression free survival	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	1 years	No