- 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.
Mesothelioma
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
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.
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.
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.
Combination Gene Transfer and Chemotherapy
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.
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.
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.
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
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Investigator’s Choice: one of the following single-agent chemotherapy might be administered in combination:
- Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
- Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
- 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
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Investigator’s Choice: one of the following single-agent chemotherapy might be administered in combination:
- Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
- Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
- 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)
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.
