Purpose: MPM patients not eligible for surgical procedures like decortication or pleuro-pneumectomy have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP which serves as target structure in MPM.
Pleural Mesothelioma
Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma.
Purpose: HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5.
Malignant mesothelioma is an aggressive, asbestos-related tumour of the pleural and peritoneal cavities. It is a rare cancer which occurs in individuals who have been exposed to asbestos, although it typically occurs decades after exposure (10-40 years later). Malignant pleural mesothelioma forms plaques that are distributed on the surface of the pleural space in the lung. Approximately 30% of patients require an indwelling pleural catheter for drainage of pleural effusions. In this patient group, the indwelling catheter may be used to facilitate loco-regional delivery of HSV1716 to the pleural space.
This study seeks to evaluate the safety and biological effects of single and multiple administrations of HSV1716 in the treatment of malignant pleural mesothelioma.
CRS-207 Cancer Vaccine in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma
Purpose: This clinical trial will evaluate the safety and immune response of the sequential administration cancer vaccine CRS-207 followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such asmesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or objective tumor response.
- Experimental Arm: Vaccine plus chemotherapy
- Weeks 1 and 3: CRS-207 (1 × 10^9 CFU)
- Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): Pemetrexed (500 mg/m2) and cisplatin (75 mg/m2)
- Weeks 23 and 26: CRS-207
- Maintenance Vaccinations: CRS-207 every 16 weeks (starting at Week 30) until disease progression
- Assigned Interventions: Biological: Vaccine plus chemotherapy
- CRS-207
- Listeria
- Pemetrexed
- Cisplatin
- ALIMTA
- Platinol
The Anti-CTLA-4 Monoclonal Antibody Tremelimumab in Malignant Mesothelioma
Rational: Preliminary results fron the Study MESOT-TREM-2012 indicate a promising activity of tremelimumab in malignant mesothelioma (MM) patients.
Purpose: The proposed study MESOT-TREM-2012 aims to explore the efficacy of a more intensive schedule of treatment with tremelimumab in 29 MM patients. Subjects will receive investigational product every 4 weeks (wks) for 6 doses, followed by doses every 12 wks until confirmed disease progression.
- Experimental Arm: single arm with Tremelimumab
- Tremelimumab: 10mg/Kg ev day 1 every 4 weeks for 6 doses in induction phase, then every 12 weeks in maintenance phase until disease progression of severe toxicity
- Assigned Intervention:
- Drug: Tremelimumab
Tremelimumab is administered as endovenous infusion - Other Name: CP-675,206
- Drug: Tremelimumab
Intracavitary Cisplatin-Fibrin Localized Chemotherapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma
Purpose: The aim is to introduce a new therapeutic method of intracavitary chemotherapy (cisplatin) combined with a fibrin carrier (Vivostat®) after pleurectomy/decortication in a phase I and IIa study for Malignant Pleural Mesothelioma patients by evaluation of the safety in a dose-escalating model.
Safety and Efficacy of Oshadi D and Oshadi R for Malignant Mesothelioma Treatment
Purpose: Malignant mesothelioma is a rare neoplasm that arises most commonly from the mesothelial surfaces of the pleural cavity, occasionally from the peritoneal surface, and rarely from the tunica vaginalis or pericardium. It has an extremely poor prognosis with a median survival of 4 to 13 months for untreated patients 1 and 6 to 18 months for treated patients, regardless of the therapeutic approach.
The anticancer activity of Oshadi D and Oshadi R treatment was tested in preclinical studies and in phase I clinical study. Four metastatic mesothelioma patients are treated for 5 to 12 months. The Oshadi D and Oshadi R combination treatment was generally well-tolerated with no dose-limiting toxicities observed.
Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum
Purpose: Increasing evidence indicates that activation of stem cell gene expression is a common mechanism by which environmental carcinogens mediate initiation and progression of thoracic malignancies. Similar mechanisms appear to contribute to extra-thoracic malignancies that metastasize to the chest. Utilization of pharmacologic agents, which target gene regulatory networks mediating stemness may be novel strategies for treatment of these neoplasms. Recent studies performed in the Thoracic Oncology Laboratory, SB/NCI, demonstrate that under exposure conditions potentially achievable in clinical settings, mithramycin diminishes stem cell gene expression and markedly inhibits growth of lung and esophageal cancer and MPM cells in vitro and in vivo. These finding add to other recent preclinical studies demonstrating impressive anti-tumor activity of mithramycin in epithelial malignancies and sarcomas that frequently metastasize to the thorax.
PIT: Prophylactic Irradiation of Tracts in Patients With Malignant Pleural Mesothelioma
Purpose: The PIT (Prophylactic Irradiation of Tracts) trial will determine whether or not PIT radiotherapy is effective in preventing or delaying the onset of chest nodules in patients with Mesothelioma.
- Arm: Experimental: PIT Arm
- Radiation: Prophylactic Irradiation of Tracts (PIT)
21 Gy in 3 fractions
Other Name: Radiation - Arm: No Intervention: No PIT Arm
Ganetespib With Pemetrexed-cisplatin, in Patients With Malignant Pleural Mesothelioma (MESO-02)
Purpose: Malignant pleural mesothelioma (MPM) is a rapidly lethal cancer arising from the parietal pleural mesothelium, and is associated with exposure to asbestos.
Once a rare disease, it is increasing in incidence in the UK and is presently more common than cervical cancer. MPM is characterized by local invasion of adjacent structures including the chest wall, mediastinum, diaphragm and pericardium resulting in progressive shortness of breath.
Median survival with best supportive care alone is approximately 6-9 months and most cases of mesothelioma present in the advanced setting. Therefore this trial will be looking at whether a new drug, Ganetespib has any improvement on survival for these types of patients.
A Phase II Trial to Assess TroVax® Plus Chemotherapy in Patients With Malignant Pleural Mesothelioma (SKOPOS)
Purpose: This study is for patients with malignant mesothelioma of the lung lining (called pleura) who are planning to have pemetrexed-cisplatin chemotherapy.
We are investigating whether giving a vaccine called TroVax® with pemetrexed-cisplatin chemotherapy is both safe and potentially beneficial in patients with mesothelioma. This vaccine has been used in combination with chemotherapy in other types of cancer and has been shown to be safe. Cancer vaccines work by stimulating the person’s immune system to fight the disease, in a similar way to the immune system fighting infection. In laboratory experiments, the vaccine has been shown to stimulate an immune response to a particular protein widely found on mesothelioma cells called 5T4. In patients with mesothelioma it is hoped that the vaccine will stimulate the immune system to attack mesothelioma cells carrying the 5T4 protein.
Pemetrexed-cisplatin chemotherapy is currently seen as the best treatment for patients with mesothelioma, and this is why we plan to combine it with the vaccine. It is hoped that the combination of the TroVax® vaccine and chemotherapy is more beneficial than chemotherapy alone.
Pemetrexed-cisplatin will be given into a vein in the arm (intravenously) every 3 weeks. The TroVax® vaccine will be given as an injection into the shoulder muscle (intramuscularly) 3 weeks before chemotherapy starts, one week before chemotherapy starts, then every 3 weeks. Each participant will receive 4 chemotherapy and 9 vaccine treatments if they complete the planned trial schedule. We aim to recruit 26 patients into the trial over a two year period. If this study shows that pemetrexed-cisplatin chemotherapy plus the TroVax® vaccine is safe and beneficial in terms of stimulating the immune system, the combination will be tested further in larger clinical trials.
- Arms: Experimental: TroVax®
- In this single-arm study, all participants will receive 9 injections of the TroVax® vaccine, plus standard cisplatin and pemetrexed chemotherapy.
- Interventions
- Biological: TroVax®: Dose of 1 x 10^9 TCID 50/ml, in 1ml, given on day 1 of weeks 1, 3, 6, 9, 12, 15, 18, 21, 24.
- Drug: Pemetrexed
500 mg/m^2 over 10 mins, given on day 3 of weeks 4, 7, 10, 13. - Drug: Cisplatin
75mg/m^2 over 1 hour, given on day 3 of weeks 4, 7, 10, 13 - Dietary Supplement: Vitamin B12
1000μg intramuscular, Day 2 of weeks 3 and 12 - Dietary Supplement: Folic Acid
400μg oral daily from Day 2 of week 3 to Day 2 of week 16 - Drug: Dexamethasone
4mg BD, Days 2-6 of weeks 4, 7, 10, 13
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