Clinical trial NCT01649024: A Clinical Study With Tremelimumab as Monotherapy 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Malignant Mesothelioma
Keywords: Tremelimumab
Malignant Mesothelioma
anti-CTLA-4 mAb
Lead sponsor: Azienda Ospedaliera Universitaria Senese
Sponsor class: OTHER
First posted: 2012-07-25
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective tumor response by modified Response Evaluation Criteria in Solid Tumor (RECIST)
timeFrame: Weeks 24
Secondary outcomes:
measure: Disease control rate
timeFrame: 1 year
measure: Progression free survival
timeFrame: 1 year
measure: Safety
timeFrame: 2 years
Other outcomes:
Locations:
city: Siena
country: Italy
facility: Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Study officials:
affiliation: Medical Oncology and Immunotherapy Unit, University Hospital of Siena
name: Michele Maio, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calabro L, Morra A, Fonsatti E, Cutaia O, Amato G, Giannarelli D, Di Giacomo AM, Danielli R, Altomonte M, Mutti L, Maio M. Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2013 Oct;14(11):1104-1111. doi: 10.1016/S1470-2045(13)70381-4. Epub 2013 Sep 11.