Please select the eligibility criteria that correspond to the clinical trial below.
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
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.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant pleural mesothelioma

  * All subtypes allowed
* T1-3, N0-1, M0 disease

  * No N2 or N3 involvement confirmed by mediastinoscopy within 21 days before study entry
* No clinical invasion of mediastinal structures (e.g., heart, aorta, spine, esophagus)
* No wide-spread chest wall invasion except focal chest wall lesions
* No clinical or radiological evidence of shrinking hemithorax
* No clinically significant third-space fluid (e.g., pleural effusions or ascites) that cannot be managed with thoracentesis or pleurodesis

PATIENT CHARACTERISTICS:

Age

* Under 70

Performance status

* WHO 0-1

Life expectancy

* Not specified

Hematopoietic

* WBC \> 3,500/mm\^3
* Absolute neutrophil count \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Hemoglobin ≥ 11 g/dL

Hepatic

* AST and ALT \< 1.5 times upper limit of normal (ULN)
* Bilirubin \< 1.5 times ULN
* Alkaline phosphatase \< 1.5 times ULN

Renal

* Creatinine clearance ≥ 60 mL/min
* Acceptable (predicted) post-radiotherapy renal function by semiquantitative isotope renography, with a relative contribution of the contralateral kidney of ≥ 40%

Pulmonary

* See Disease Characteristics

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 3 months after completion of study treatment
* Deemed to be fit enough to undergo study treatment
* No preexisting sensory neurotoxicity \> grade 1
* No uncontrolled infection
* No prior or concurrent melanoma, breast cancer, or hypernephroma
* No other malignancy within the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy
* No concurrent routine use of colony-stimulating factors during neoadjuvant chemotherapy

  * Concurrent secondary prophylactic use allowed during neoadjuvant chemotherapy
* No concurrent secondary prophylactic use of colony-stimulating factors during post-operative radiotherapy

Chemotherapy

* No prior chemotherapy for mesothelioma

Endocrine therapy

* No concurrent hormonal cancer therapy

Radiotherapy

* No prior radiotherapy to the lower neck, thorax, or upper abdomen

Surgery

* See Disease Characteristics

Other

* No other concurrent anticancer therapy
* No other concurrent experimental medications
* No nonsteroidal anti-inflammatory drugs or salicylates for 2 days before, during, and 2 days after administration of neoadjuvant chemotherapy (5 days before and 2 days after for drugs with a long half-life \[e.g., naproxen, piroxicam, diflunisal, or nabumetone\])
B: Inclusion Criteria:

* Malignant, histologically proved, non resectable pleural Mesothelioma
* In case of pleural effusion, a talc pleurodesis, although not recommended, is allowed in accordance with current local practice, at the time of diagnostic thorascopy, with inclusion CT scan performed after pleurodesis.
* ECOG Performance status 0-2
* Mesothelioma with only pleural effusion without uni- or bidimensionally measurable disease will be eligible (adapted RECIST criteria)
* At least 18 years of age, less than 76 years of age
* Radiation therapy of thoracocentis tract (3 x 7Gy) performed before beginning medical study treatment, and the interval between thoracoscopic procedure and radiation will not exceed 28 days

Exclusion Criteria:

* Prior chemotherapy
* Brain metastasis
* History of cerebral vascular accident (CVA) or transient ischemic attack
C: 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
D: 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

Answer: C