Clinical Trials

Dendritic Cell-based Immunotherapy Combined With Low-dose Cyclophosphamide in Patients With Malignant Mesothelioma (PMR-MM-002)

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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A Study in Non Small Cell Lung Cancer

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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Radical Pleurectomy/Decortication (PD) and Intensity Modulated Radiotherapy (IMRT)

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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Quality of Life and Survivorship Care in Patients Undergoing HIPEC (HOPE)

Rationale: An orientation and patient education program and telephone counseling may help improve the quality of life in patients with peritoneal surface malignancies.

Purpose: This clinical trial studies quality of life and survivorship care in patients undergoing surgery and chemotherapy for peritoneal surface malignancies.

Arm I: Experimental
Patients and their caregiver(s) receive a hyperthermic intraperitoneal chemotherapy (HIPEC) orientation with a Survivorship Navigator (SN) over 90 minutes following their initial surgical consult. Patients then receive telephone calls over 20-30 minutes from the SN once weekly for 3 weeks prior to HIPEC. After HIPEC, patients meet with the SN for 20-30 minutes to discuss adjustments and adaptation to the surgery and hospitalization 3-4 days post-HIPEC, biweekly for two weeks and weekly thereafter until hospital discharge. After hospital discharge, patients receive telephone calls from the SN twice monthly for 1 month.

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Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma

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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AMG 102, Pemetrexed Disodium, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma

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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NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed

Purpose: The main objective of the trial is to document the efficacy of NGR-hTNF administered at low dose weekly in advanced Malignant Pleural Mesothelioma patients previously treated with a pemetrexed-based chemotherapy regimen.

Arm A: NGR-hTNF + BIC: Experimental; Intervention: Drug: NGR-hTNF plus Best Investigator Choice (BIC)
Drug: NGR-hTNF plus Best Investigator Choice (BIC)

  • NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator’s Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Arm B: Placebo+BIC: Placebo Comparator; Intervention: Drug: Placebo plus Best Investigator Choice (BIC)
Drug: Placebo plus Best Investigator Choice (BIC)

  • Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.
  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator’s Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

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Pemetrexed Disodium or Observation in Treating Patients With Malignant Pleural Mesothelioma Without Progressive Disease After First-Line Chemotherapy

Rationale: pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Purpose: This randomized phase II trial is studying how well pemetrexed disodium or observation works in treating patients with malignant pleural mesothelioma without progressive disease after first-line chemotherapy.

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Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma

Rationale: Drugs used in chemotherapy, 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. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving pemetrexed disodium and cisplatin together with cediranib maleate may kill more tumor cells.

Purpose: This randomized phase I/II trial is studying the side effects and best dose of cediranib maleate when given together with pemetrexed disodium and cisplatin and tp see how well it works in treating patients with malignant pleural mesothelioma.

Arm I (phase II): Experimental
Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and oral cediranib maleate once daily at the maximum tolerated dose determined in phase I on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate, Given orally
Drug: cisplatin, Given IV
Drug: pemetrexed disodium, Given IV
Arm II (phase II): Active Comparator
Patients receive pemetrexed disodium and cisplatin as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral placebo alone once daily in the absence of disease progression or unacceptable toxicity.
Drug: cisplatin, Given IV
Drug: pemetrexed disodium, Given IV
Other: placebo, Given orally

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