Purpose: Earlier the investigators determined the safety and feasibility of tumor lysate-pulsed dendritic cells as therapeutic adjuvants in mesothelioma patients. Because pre-clinical data in mice had shown that better results were obtained when regulatory T cells were depleted using low-dosis of cyclophosphamide, ten patients who responded on chemotherapy are selected for DC-treatment in combination with Endoxan.

DC immunotherapy + CTX: Experimental

Patients with mesothelioma who are fit enough to be treated with chemotherapy and enough tumor material was available are asked for participation in this study. After 4 cycles of Alimta chemotherapy, a leukapheresis is performed of which the monocytes are used for differentiation to DCs using different cytokines. The procedure to grow DCs in vitro and pulse them with tumor lysate is performed according to our earlier performed phase I study that was approved by our local ethics committee. Three doses of properly pulsed autologous DCs (MesoCancerVac) are then re-injected every two weeks. Patients will be treated with a low dose of CTX for seven day in a row the week before the 1st vaccination, the weeks in between the 2nd, and for one week after the 3rd vaccination.

Intervention: Biological: DC + CTX

3x 50x10e6 DC + cyclophosphamide

Other Name: Endoxan

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Purpose: LY2603618 is a potent and selective inhibitor of the deoxyribonucleic acid (DNA) damage checkpoint kinase 1 (Chk1). It is being developed as a chemotherapeutic-enhancing agent in the treatment of cancer. Ongoing Phase 1 studies have shown the feasibility of combining LY2603618 with either gemcitabine or pemetrexed. The objective of this study is to find the dose of LY2603618 that can be safely combined with standard doses of pemetrexed and cisplatin and to test if this triplet offers a significant improvement in progression-free survival in patients with Stage IV nonsquamous non-small cell lung cancer (NSCLC) in the first-line of palliative treatment.

Arms:

Phase 1: Experimental

Cycle 1-2 (21 day cycle):

• Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2
• Day 2: LY2603618 40 – 150 mg/m2

After 2 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.

Phase 2: Pemetrexed + Cisplatin + LY2603618: Experimental

Cycle 1-6 (21 day cycle):

• Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2
• Day 2: LY2603618 dose determined from phase 1 portion of trial

After 6 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.

Phase 2: Pemetrexed + Cisplatin: Active Comparator

Cycle 1-6 (21 day cycle):

• Day 1: Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2

After 6 cycles, patients may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met.

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Purpose: The goal of this clinical research study is to find the highest tolerable dose of radiation that can be given to directly to the pleura (the outer lining of the lungs) using intensity modulated radiation therapy (IMRT) in patients with malignant mesothelioma (MM) who have had a pleurectomy.

Arm I: IMRT: Experimental

Radiation: IMRT

Delivery of whole-pleura radiation doses beginning with 1) 45 Gy to low-risk region and 60-66 Gy to high-risk region; then 2) the same dosing regimen as above with a third dosing level, 50 Gy to an intermediate-dosing region. Every weekday (Monday-Friday) for up to 5 weeks, lasting about 45-60 minutes.

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Purpose: The purpose of this study is to find the safety of combination gene therapy and chemotherapy in patients with malignant pleural mesothelioma. Pleural catheter will be placed first, then pts will receive 2 doses of intrapleural vector followed by front line or second line chemotherapy 4-6 cycles every 21 days.

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Purpose: This study is being conducted to evaluate the overall safety and effectiveness of an investigational drug, GC1008, in patients with mesothelioma. An investigational drug is one that has not been approved by the FDA. Approximately 40 people will be enrolled on this study at the University of Pennsylvania (Main Institution/Coordinating Site) and the University of Chicago (Participating Institution). We expect about 20 subjects to be enrolled at each institution.

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Rationale: Monoclonal antibodies, such as AMG 102, can block tumor growth in different ways. Some block the ability of tumor cells to grow or spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AMG 102 together with pemetrexed disodium and cisplatin may kill more tumor cells.

Purpose: This phase II trial is studying how well giving AMG 102 together with pemetrexed disodium and cisplatin works in treating patients with malignant pleural mesothelioma.

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Purpose: For patients with malignant pleural mesothelioma that has grown despite treatment with standard chemotherapy, no treatment has yet proven beneficial. The purpose of this study is to find out what effects, both good and bad, that everolimus has on the cancer. Everolimus works by blocking a protein that helps the cancer grow. The goal of this clinical research study is to learn if the study drug everolimus can shrink or slow the growth of mesothelioma. The safety of this drug will also be studied. The patients’ physical state, changes in the size of the tumor, and laboratory findings taken during the study will help us decide if everolimus is safe and effective.

Arms: Pts getting everolimus: Experimental

This is a single institution, open label, phase II study of everolimus as a second or third line therapy for the treatment of advanced malignant pleural mesothelioma, which will also evaluate Merlin/NF2 loss as a biomarker to predict sensitivity to everolimus. Patients who have disease progression after one or two prior chemotherapy regimens will be eligible. In the first stage of this design, 19 patients will be accrued. If 6 or less patients among the first 19 patients show clinical benefit, then the study will be terminated and declared negative. If 7 or more patients show clinical benefit, than an additional 20 patients will be accrued to the second stage. At the end of the study, if 17 or more patients show clinical benefit out of a total of 39 patients enrolled, the regimen will be considered worthy of further investigation.

Drug: everolimus. Everolimus will be administered at a dose of 10mg orally once daily continuously. Dose reduction may be required depending on the type and severity of toxicity encountered. One cycle will be considered 28 days. Patients will have CT scans to evaluate for response after cycle 1 and cycle 2, and then every two cycles thereafter.

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