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.
Status
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
A Study of LY3023414 in Participants With Advanced Cancer
Purpose: The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer, including but not limited to lymphoma, breast cancer, and mesothelioma. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Finally, the study will help document any antitumor activity this drug may have.
In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3023414. In Part B, LY3023414 will be explored in different types of cancer, including breast cancer and mesothelioma.
- Experimental Arm: Part A: LY3023414 Once Daily
- LY3023414 administered orally once daily (QD) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
- Assigned Interventions:
- Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
- Drug: LY3023414
- Experimental Arm: Part A2: LY3023414 Twice Daily
- LY3023414 administered orally twice daily (BID) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
- Assigned Interventions:
- Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
- Drug: LY3023414
- Experimental Arm: Part B1 : LY3023414 + Midazolam
- LY3023414 administered orally QD or BID for two 21 day cycles to participants with advanced/metastatic cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 0.2 mg midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
- Assigned Interventions:
- Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A. - Drug: Midazolam
0.2 mg administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
- Drug: LY3023414
- Experimental Arm: Part B2: LY3023414 + Letrozole
- LY3023414 administered orally QD or BID for two 21 day cycles to participants with advanced/metastatic breast cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 25 mg Letrozole administered orally QD.
- Assigned Interventions:
- Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A. - Drug: Letrozole
25 mg administered orally QD.
- Drug: LY3023414
- Experimental Arm: Part B3: LY3023414
- LY3023414 administered orally QD or BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A.
- Assigned Interventions: Drug: LY3023414
Administered orally QD or BID for a 21 day Cycle. Dose of 20 to 600 mg, as determined in Part A.
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.
Register With Patients in Which Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) Was Performed
Purpose: The purpose of this study is to register the follow-up data of patients who, because of a peritoneal surface malignancy, will undergo cytoreductive surgery and HIPEC.
- Registry
- Patients with peritoneal carcinomatosis of colorectal origin, patients with pseudomyxoma peritonei (type DPAM or PMCA) and patients with peritoneal mesothelioma who are planned to undergo cytoreductive surgery and HIPEC because of a peritoneal surface malignancy
A Study of HGS1036 in Combination With Chemotherapy in Subjects With Advanced Solid Malignancies
Purpose: The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, docetaxel, or pemetrexed.
- Experimental; Arm A: HGS1036 + Paclitaxel + Carboplatin
- Drug: HGS1036 + Paclitaxel + Carboplatin
HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle. Paclitaxel 175 mg/m2 or 200 mg/m2, IV and carboplatin AUC 6.0 mg∙min/mL, IV every 3 weeks on Day 1 of each 21-day cycle. - Experimental; Arm B:
HGS1036 + Cisplatin + Etoposide - Drug: HGS1036 + Cisplatin + Etoposide
HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle and cisplatin 60-80 mg/m2, IV on Day 1 and etoposide 100-120 mg/m2, IV on Days 1, 2, and 3 of each 21 day cycle. - Experimental; Arm C:
HGS1036 + Docetaxel - Drug: HGS1036 + Docetaxel
HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle and docetaxel 75 mg/m2, IV on Day 1 of each 21-day cycle. - Experimental; Arm D:
HGS1036 + Pemetrexed - Drug: HGS1036 + Pemetrexed
HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle and pemetrexed 500 mg/m2, IV on Day 1 of each 21-day cycle.
