The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma

NCT ID: NCT01655888

Last Updated: 2012-08-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-01-31

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:

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

Conditions

Malignant Mesothelioma

Keywords

Tremelimumab; anti-CTLA-4 monoclonal antibody; malignant mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Tremelimumab

Intervention Type: DRUG

Tremelimumab is administered as endovenous infusion

Interventions

Tremelimumab

Tremelimumab is administered as endovenous infusion

Intervention Type: DRUG

Other Intervention Names

CP-675,206

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: collaborator

Azienda Ospedaliera Universitaria Senese

OTHER

Sponsor Role: lead

Responsible Party

Michele Maio

Head of Medical Oncology and Immunotherapy Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michele Maio, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology and Immunotherapy Unit, University Hospital of Siena, Italy

Luana Calabrò, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology and Immunotherapy, University Hospital of Siena, Italy

Locations

Medical Oncology and Immunotherapy Unit, University Hospital of Siena

Siena, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Michele Maio, MD

Role: CONTACT

Phone: +39-0577586335

Email: mmaio@cro.it

Luana Calabrò, MD

Role: CONTACT

Phone: +39-0577586116

Email: l.calabro@ao-siena.toscana.it

Facility Contacts

Michele Maio, MD

Role: primary

Luana Calabrò, MD

Role: backup

References

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.

Reference Type: DERIVED

PMID: 25819643 (View on PubMed)

Other Identifiers

2012-002762-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MESOT-TREM-2012

Identifier Type: -

Identifier Source: org_study_id