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
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
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
NCT ID
NCT01655888
First Posted
July 31, 2012
Last Updated
July 31, 2012
Sponsor
Azienda Ospedaliera Universitaria Senese
Collaborators
MedImmune LLC
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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