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.

Study Overview

• Status: Unknown
• Conditions: Malignant Mesothelioma
• Intervention / Treatment: Drug: Tremelimumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: CP-675,206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Weeks 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year
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.	3 years
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	1 years

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera Universitaria Senese
• Collaborators: 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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Anticipated): January 1, 2014
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: July 31, 2012
• First Submitted That Met QC Criteria: July 31, 2012
• First Posted (Estimate): August 2, 2012

Study Record Updates

• Last Update Posted (Estimate): August 2, 2012
• Last Update Submitted That Met QC Criteria: July 31, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Tremelimumab; malignant mesothelioma; anti-CTLA-4 monoclonal antibody
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Antineoplastic Agents; Tremelimumab
• Other Study ID Numbers: MESOT-TREM-2012; 2012-002762-12 (EudraCT Number)