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

Brief Title

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

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

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
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

To determine the objective response

Secondary Outcome

 Disease control rate (DCR)

Condition

Malignant Mesothelioma

Intervention

Tremelimumab

Study Arms / Comparison Groups

 single arm with Tremelimumab

Description:  Tremelimumab: 10mg/Kg ev day 1 every 4 weeks for 6 doses in induction phase, then every 12 weeks in maintenance phase until disease progression of severe toxicity

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

29

Start Date

July 2012

Completion Date

January 2015

Primary Completion Date

January 2014

Eligibility 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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Michele Maio, MD, +39-0577586335, [email protected]

Location Countries

Italy

Location Countries

Italy

NCT ID

NCT01655888

Organization ID

MESOT-TREM-2012

Secondary IDs

2012-002762-12

Responsible Party

Principal Investigator

Study Sponsor

Azienda Ospedaliera Universitaria Senese

Collaborators

 MedImmune LLC

Study Sponsor

Michele Maio, MD, Principal Investigator, Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Italy

Verification Date

July 2012