The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Malignant Mesothelioma	Drug: Tremelimumab	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Mesothelioma

U.S. FDA Resources

Further study details as provided by Azienda Ospedaliera Universitaria Senese:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment:	29
Study Start Date:	July 2012
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	Drug: Tremelimumab Tremelimumab is administered as endovenous infusion Other Name: CP-675,206

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655888

Contacts

Contact: Michele Maio, MD	+39-0577586335	mmaio@cro.it
Contact: Luana Calabrò, MD	+39-0577586116	l.calabro@ao-siena.toscana.it

Locations

Italy
Medical Oncology and Immunotherapy Unit, University Hospital of Siena	Recruiting
Siena, Italy, 53100
Contact: Michele Maio, MD +39-0577586335 mmaio@cro.it
Contact: Luana Calabrò, MD +39-0577586116 l.calabro@ao-siena.toscana.it
Principal Investigator: Michele Maio, MD
Sub-Investigator: Luana Calabrò, MD

Sponsors and Collaborators

Azienda Ospedaliera Universitaria Senese

MedImmune LLC

Investigators

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

More Information

No publications provided

Responsible Party:	Michele Maio, Head of Medical Oncology and Immunotherapy Unit, Azienda Ospedaliera Universitaria Senese
ClinicalTrials.gov Identifier:	NCT01655888 History of Changes
Other Study ID Numbers:	MESOT-TREM-2012, 2012-002762-12
Study First Received:	July 31, 2012
Last Updated:	July 31, 2012
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Azienda Ospedaliera Universitaria Senese:

Tremelimumab
anti-CTLA-4 monoclonal antibody
malignant mesothelioma

Additional relevant MeSH terms:

Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial

Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013