A Clinical Study With Tremelimumab as Monotherapy in Malignant Mesothelioma

Phase 2

• Conditions: Malignant Mesothelioma
• Interventions: Drug: Tremelimumab

• Registration Number: NCT01649024
• Lead Sponsor: Azienda Ospedaliera Universitaria Senese

Brief Summary

The study is designed to define the immunologic and clinical activity of Tremelimumab in patients with advanced mesothelioma.

Detailed Description

No effective standard treatment can improve significantly the prognosis of malignant mesothelioma (MM) patients. However, there is evidence that MM patients may benefit from immunotherapeutic agents.

Clinical studies examining CTLA-4 blockade are providing convincing evidences on the immunobiological effects and on the clinical activity of this new class of immunomodulating therapeutic agents, likely due to their ability to stimulate patients'immune system to more effectively attack tumor cells by blocking a negative regulatory signal.

Tremelimumab is a fully human anti-CTLA-4 monoclonal antibody (mAb), developed as an IgG2 isotype to minimize complement activation and reduce the risk of cytokine storm. As a single agent, Tremelimumab can induce durable tumor regression in 7-10% of patients with advanced melanoma. Tremelimumab has been tested in several clinical trials as single-agent or in combination with other agents in different solid tumors.

The evidences above unveil a strong immunologic potential of treatment with Tremelimumab also in MM patients.

Study Timeline

• Study Start: 2009-05
• Primary Completion: 2012-06
• Status Verified: 2012-07
• Study First Submitted: 2012-07-18
• Study First Submitted QC: 2012-07-20
• Last Update Submitted: 2012-07-20
• Study First Posted: 2012-07-25
• Last Update Posted: 2012-07-25
• Study Completion: 2013-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Histologically or cytologically confirmed malignant mesothelioma (MM)
• Have received only one prior systemic chemotherapy platinum-based regimen for advanced MM
• 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
• Not pregnant or nursing
• 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
• Clinically relevant cardiovascular disease, i.e., myocardial infarction or other severe coronary artery diseases within the prior 6 months, cardiac arrythmia requiring medication, uncontrolled hypertension, overt cardiac failure or not compensated chronic heart disease in NYHA class II or more
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm of Tremelimumab	Tremelimumab	Tremelimumab is administered at 15 mg/kg on day 1 every 12 weeks for 4 doses

Primary Outcome Measures

Name	Time	Method
Objective tumor response by modified Response Evaluation Criteria in Solid Tumor (RECIST)	Weeks 24	The objective tumor response is defined as a confirmed complete response (CR) or partial response (PR) according to the modified RECIST criteria for pleural mesothelioma

Secondary Outcome Measures

Name	Time	Method
Disease control rate	1 year	Disease control rate (DCR) is the proportion of treated subjects that achieved confirmed complete response, or partial response, or stable disease.; The DCR is assessed using the modified RECIST criteria for pleural mesothelioma
Progression free survival	1 year	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
Safety	2 years	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 physical examination findings are also included.

Trial Locations

Locations (1)

Medical Oncology and Immunotherapy Unit, University Hospital of Siena; 🇮🇹 Siena, Italy