Pleural Mesothelioma
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
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.
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.
- Background:
- IMC-A12, a new cancer treatment that has not yet been approved by the U.S. Food and Drug Administration, is an antibody that is designed to block the effects of a protein called Type I Insulin-Like Growth Factor (IGF-1R). IMC-A12 blocks the receptors in cells that respond to IGF-1R, which are thought to play an important role in helping cancer cells to grow and divide. Researchers are interested in determining whether IMC-A12 is an effective treatment for individuals who have mesothelioma that has not responded to standard chemotherapy.
- Objectives:
- To evaluate the safety and effectiveness of IMC-A12 treatment in individuals with mesothelioma who have previously had chemotherapy.
- Eligibility:
- Individuals at least 18 years of age who have been diagnosed with mesothelioma that has not responded to chemotherapy.
- Design:
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- * Eligible participants will be screened with a full physical examination and medical history, blood and urine samples, and imaging studies.
- * Participants will receive IMC-A12 once every 3 weeks (21-day cycle), and will be evaluated before the start of each new cycle with blood tests and imaging studies if needed.
- * Treatment cycles will continue for as long as needed, unless severe side effects develop or the disease progresses.
- Background:
- Certain types of lung, esophageal, or thymic cancers and mesotheliomas have specific antigens (protein molecules) on their surfaces. Research studies have shown that giving a vaccine that contains antigens similar to these may cause an immune response, which may keep tumors from growing. Researchers are also interested in determining whether the chemotherapy drug cyclophosphamide and the anti-inflammatory drug celecoxib may help the vaccine work better, particularly in patients with lung cancer.
- Objectives:
- To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.
- Eligibility:
- Individuals at least 18 years of age who have had surgery for small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, and malignant pleural mesothelioma.
- Design:
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- Following recovery from surgery, chemotherapy, or radiation, participants will have leukapheresis to collect lymphocytes (white blood cells) for testing.
- Participants will receive celecoxib and cyclophosphamide to take twice a day at home, 7 days before the vaccine.
- Participants will have the vaccine in the clinical center (one or two shots per month for 6 months), and will stay in the clinic for about 4 hours after the vaccine. Participants will keep a diary at home of any side effects from the vaccine, and will continue to take cyclophosphamide and celecoxib.
- One month after the sixth vaccine, participants will provide another blood sample for testing, and if the tests are satisfactory will return to the clinic every 3 months for 2 additional vaccines.
- Participants will return to clinic for follow-up physical examinations, lab tests, and scans every 3 months for 2 years and then every 6 months for up to 3 years.
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
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.
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.
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.
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.
