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

Primary Purpose

Malignant Mesothelioma

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Tremelimumab
Sponsored by
Azienda Ospedaliera Universitaria Senese
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Mesothelioma focused on measuring Tremelimumab, anti-CTLA-4 monoclonal antibody, malignant mesothelioma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Medical Oncology and Immunotherapy Unit, University Hospital of SienaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm with Tremelimumab

Arm 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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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.
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

Full Information

First Posted
July 31, 2012
Last Updated
July 31, 2012
Sponsor
Azienda Ospedaliera Universitaria Senese
Collaborators
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01655888
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Unknown status
Study Start Date
July 2012 (undefined)
Primary Completion Date
January 2014 (Anticipated)
Study Completion Date
January 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliera Universitaria Senese
Collaborators
MedImmune LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: To define toxicity profile according to NCI CT-CAE V. 3 To assess the overall survival (OS) To estimate disease control rate (DCR) (proportion of patients with best response of CR+PR+SD) according to the modified Recist criteria To assess the progression-free survival in treated patients according to modified Recist criteria To evaluate qualitative and quantitative changes in cellular and humoral immune responses

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Mesothelioma
Keywords
Tremelimumab, anti-CTLA-4 monoclonal antibody, malignant mesothelioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
single arm with Tremelimumab
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Tremelimumab
Other Intervention Name(s)
CP-675,206
Intervention Description
Tremelimumab is administered as endovenous infusion
Primary Outcome Measure Information:
Title
To determine the objective response
Description
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
Time Frame
Weeks 24
Secondary Outcome Measure Information:
Title
Disease control rate (DCR)
Description
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
Time Frame
1 year
Title
Safety
Description
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.
Time Frame
3 years
Title
Progression free survival
Description
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
Time Frame
1 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michele Maio, MD
Phone
+39-0577586335
Email
mmaio@cro.it
First Name & Middle Initial & Last Name or Official Title & Degree
Luana Calabrò, MD
Phone
+39-0577586116
Email
l.calabro@ao-siena.toscana.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Maio, MD
Organizational Affiliation
Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luana Calabrò, MD
Organizational Affiliation
Medical Oncology and Immunotherapy, University Hospital of Siena, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
City
Siena
ZIP/Postal Code
53100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michele Maio, MD
Phone
+39-0577586335
Email
mmaio@cro.it
First Name & Middle Initial & Last Name & Degree
Luana Calabrò, MD
Phone
+39-0577586116
Email
l.calabro@ao-siena.toscana.it
First Name & Middle Initial & Last Name & Degree
Michele Maio, MD
First Name & Middle Initial & Last Name & Degree
Luana Calabrò, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
25819643
Citation
Calabro L, Morra A, Fonsatti E, Cutaia O, Fazio C, Annesi D, Lenoci M, Amato G, Danielli R, Altomonte M, Giannarelli D, Di Giacomo AM, Maio M. Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study. Lancet Respir Med. 2015 Apr;3(4):301-9. doi: 10.1016/S2213-2600(15)00092-2. Epub 2015 Mar 26.
Results Reference
derived

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

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