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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by Azienda Ospedaliera Universitaria Senese
Sponsor:
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
Michele Maio, Azienda Ospedaliera Universitaria Senese
ClinicalTrials.gov Identifier:
NCT01655888
First received: July 31, 2012
Last updated: NA
Last verified: July 2012
History: No changes posted

July 31, 2012
July 31, 2012
July 2012
January 2014   (final data collection date for primary outcome measure)
To determine the objective response [ Time Frame: Weeks 24 ] [ Designated as safety issue: No ]
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
Same as current
No Changes Posted
  • Disease control rate (DCR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 years ] [ Designated as safety issue: No ]
    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
Same as current
Not Provided
Not Provided
 
The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma
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

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.

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
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Mesothelioma
Drug: Tremelimumab
Tremelimumab is administered as endovenous infusion
Other Name: CP-675,206
Experimental: single arm with Tremelimumab
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
Intervention: Drug: Tremelimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
29
January 2015
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Michele Maio, MD +39-0577586335 mmaio@cro.it
Contact: Luana Calabrò, MD +39-0577586116 l.calabro@ao-siena.toscana.it
Italy
 
NCT01655888
MESOT-TREM-2012, 2012-002762-12
Yes
Michele Maio, Azienda Ospedaliera Universitaria Senese
Azienda Ospedaliera Universitaria Senese
MedImmune LLC
Principal Investigator: Michele Maio, MD Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Italy
Principal Investigator: Luana Calabrò, MD Medical Oncology and Immunotherapy, University Hospital of Siena, Italy
Azienda Ospedaliera Universitaria Senese
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP