Purpose: The role of surgical resection in the management of Malignant Pleural Mesothelioma (MPM) is still controversial. The selection criterion to perform either Extrapleural Pneumonectomy (EPP) or Pleurectomy/Decortication (P/D) is dependent not only on the cardio-pulmonary status of the patient, tumor stage and intraoperative findings but also on surgeons’ decision and philosophy. There are no established guidelines. Radical Pleurectomy (RP) competes against EPP as surgical therapy modality. Both surgical approaches are cytoreductive treatment options. The aim is to remove all gross disease and to achieve macroscopic complete resection.

Originally P/D was a palliative option for controlling pleural effusion. But lung-sparing surgery for MPM seems to be an alternative to patients unsuitable or unwilling to undergo EPP in a multimodality therapy concept. Most studies evaluating multimodality therapies for MPM are based on retrospective analyses and their interpretation is difficult because of inhomogeneous patient groups studied.

The aim of our study was to analyze the feasibility and results of RP as surgical therapy modality in a standardized trimodality therapy concept.

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Purpose: This is a randomised Phase II clinical trial to assess and compare efficacy and safety profile of cisplatin and pemetrexed against cisplatin and low-dose gemcitabine in long infusion.

Arm 1: Cisplatin with pemetrexed: Active Comparator; Intervention: Procedure: Gemcitabine in long infusion

• Procedure: Gemcitabine in long infusion
  • TREATMENT A:
    • Day 1: Pemetrexed 500 mg/m2 Cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: folic acid [Tifol 400 mg tbl (350-1000 mg), beginning 7 days before CT, every day, till 3 week after the KT], vitamin B-12 [OH-B12 i.m., beginning in 7 days before CT, than at 3. + 6. cycles of KT + 9. week after the KT], corticosteroids, hydration, antiemetic, LMW heparin as thromboprophylaxis.
    • In the absence of progression, 4 cycles of chemotherapy with pemetrexed and cisplatin will be given, followed by two additional cycles of pemetrexed as monotherapy.
  • TREATMENT B:
• Days 1 and 8: gemcitabine 250 mg/m2 in 6 hours day 2: cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: corticosteroids, hydration, antiemetics, LMW heparin as thromboprophylaxis.
• In the absence of progression, 4 cycles of chemotherapy with gemcitabine and cisplatin will be given, followed by two additional cycles of gemcitabine alone as monotherapy.

Arm 2: Cisplatin with gemcitabine in long infusion: Experimental; Intervention: Procedure: Gemcitabine in long infusion

• Procedure: Gemcitabine in long infusion
  • TREATMENT A:
    • Day 1: Pemetrexed 500 mg/m2 Cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: folic acid [Tifol 400 mg tbl (350-1000 mg), beginning 7 days before CT, every day, till 3 week after the KT], vitamin B-12 [OH-B12 i.m., beginning in 7 days before CT, than at 3. + 6. cycles of KT + 9. week after the KT], corticosteroids, hydration, antiemetic, LMW heparin as thromboprophylaxis.
    • In the absence of progression, 4 cycles of chemotherapy with pemetrexed and cisplatin will be given, followed by two additional cycles of pemetrexed as monotherapy.
  • TREATMENT B:
    • Days 1 and 8: gemcitabine 250 mg/m2 in 6 hours day 2: cisplatin 75 mg/m2 Cycle every 3 weeks. Supportive treatment: corticosteroids, hydration, antiemetics, LMW heparin as thromboprophylaxis.
    • In the absence of progression, 4 cycles of chemotherapy with gemcitabine and cisplatin will be given, followed by two additional cycles of gemcitabine alone as monotherapy.

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Purpose: The doctors are testing a Wilms Tumor-1 (WT1) vaccine to see if it delays or
prevents the mesothelioma from growing back after surgery. WT1 is a protein in cancer
cells that regulates gene expression and causes cell growth. Mesothelioma tumors
generally have high levels of WT1. The patient will be assigned to one of two treatment
groups. One group will receive non-specific immunotherapy with medications called
Montanide and Sargramostim (GM-CSF). The other group will receive more specific
immunotherapy with the WT1 vaccine plus Montanide and GM-CSF. Both Montanide and GM-CSF
are commonly given along with vaccines because they have a general effect in boosting
the immune response. Some researchers believe that this general increase in the immune
system may have some effect in treating cancer. Some studies using GM-CSF with melanoma
vaccines have suggested that it could lessen the effects of the vaccine. The addition
of the WT1 proteins makes this therapy more directed to mesothelioma. The combination
of WT1 vaccine with Montanide and GM-CSF has been tested in a prior trial including 9
patients with advanced mesothelioma. In that trial, the vaccine was safe and caused an
immune response. The patient will have a 50% chance of being in each group. Neither the
patient nor the doctor will be aware of which group they are in.

Arm: WT-1-vaccine Montanide + GM-CSF: Experimental

• The study will be a randomized phase II trial to determine the 1-year
  progression free survival after treatment with WT-1 analog peptide vaccine
  in patients with MPM after completion of combined modality therapy.
• Intervention: Biological: WT-1-vaccine Montanide + GM-CSF

Assigned Interventions: Biological: WT-1-vaccine Montanide + GM-CSF

• Patients will receive 6 injections over 12 weeks. Treatment will be
  administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive
  Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of
  each vaccination. Patients may self administer the Sargramostim (GM-CSF) on
  day -2 if they have been appropriately instructed on SQ injection
  administration. Patients will keep a logbook noting the time and placement
  of the injection. Patients will also receive 1.0 ml of emulsion with
  Montanide alone or with WT-1 peptides plus Montanide. It will be
  administered subcutaneously to the same anatomical site as the GM-CSF. This
  site will be marked by the patient or treating healthcare professional by a
  permanent marker pen.

Arm: Montanide adjuvant + GM-CSF: Active Comparator

• The study will be a randomized phase II trial to determine the 1-year
  progression free survival after treatment with WT-1 analog peptide vaccine
  in patients with MPM after completion of combined modality therapy.
• Intervention: Biological: Montanide adjuvant + GM-CSF

Assigned Interventions: Biological: Montanide adjuvant + GM-CSF

• Patients will receive 6 injections over 12 weeks. Treatment will be
  administered on weeks 0, 2, 4, 6, 8, and 10. All patients will receive
  Sargramostim (GM-CSF) (70 mcg) injected subcutaneously on days 0 and -2 of
  each vaccination. Patients may self administer the Sargramostim (GM-CSF) on
  day -2 if they have been appropriately instructed on SQ injection
  administration. Patients will keep a logbook noting the time and placement
  of the injection. Patients will also receive 1.0 ml of emulsion with
  Montanide alone or with WT-1 peptides plus Montanide. It will be
  administered subcutaneously to the same anatomical site as the GM-CSF. This
  site will be marked by the patient or treating healthcare professional by a
  permanent marker pen.

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Purpose: This research will study how to activate the immune system by using gene transfer. Gene transfer involves inserting a specially designed gene into cancer cells. A gene is a part of the genetic code that instructs the cells of our bodies to produce specific compounds (proteins) important for the makeup or function of the cell. The study hypothesis is that repeated doses of SCH 721015 given over a three day interval would result in gene transfer.

arm 1: Dose Level 1: Experimental

Biological: SCH 721015

1.0 x 10e12 viral particles on Days 1 and 4

arm 2: Dose Level 2: Experimental (This is a dose de escalation)

Biological: SCH 721015

3.0 x 10e11 viral particles on Days 1 and 4

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Purpose: The purpose of this study is to investigate the effects of axitinib, a potent angiogenesis inhibitor, on tissue and clinical outcome in combination with chemotherapy given to patients with mesothelioma.

arm 1: Active Comparator: cisplatin + premetrexed

Drug: chemotherapy

cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.

arm 2: Experimental: axitinib + cisplatin + premetrexed

Biological: axitinib

axitinib: 5 mg BID, day 2 until day 21 of each cycle; cisplatin: 75 mg/m2 day 1, every 3 weeks; pemetrexed: 500 mg/m2 day 1, every 3 weeks.

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Purpose: The primary objective of this trial is to determine the response rate of single agent zoledronic acid using a composite of criteria including the EORTC modified RECIST criteria and the EORTC tumor response criteria for 18F-FDG PET scans.

Arms

Experimental: infusion of zoledronic acid

Zoledronic acid will be administered on Day 1 of a 3-week cycle followed by tumor assessment from CT and/or PET scans every 2 cycles. This will continue until progression of disease and/or intolerable toxicity.

Drug: Zometa (zoledronic acid): Zoledronic acid will be administered IV on the first day of a 21 day cycle at a concentration of 4 mg. The treatment will take about 30-60 minutes with the infusion lasting about 15 minutes.

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