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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

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

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

Time Frame

Weeks 24

Secondary Outcome Measure Information:

Title

Disease control rate (DCR)

Description

Time Frame

1 year

Title

Safety

Description

Time Frame

3 years

Title

Progression free survival

Description

Time Frame

1 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

mmaio@cro.it

First Name & Middle Initial & Last Name or Official Title & Degree

Luana Calabrò, MD

Phone

+39-0577586116

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

mmaio@cro.it

First Name & Middle Initial & Last Name & Degree

Luana Calabrò, MD

Phone

+39-0577586116

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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