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.
Pleural Mesothelioma
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
A Phase II Study of PF-03446962 in Patients With Advanced Malignant Pleural Mesothelioma
Purpose: The purpose of this study is to find out what effects a new drug PF-03446962 has on cancer. In addition, this study will look at the side effects of PF-03446962.
BAY 94-9343 for Advanced Solid Tumors
Purpose:
- Background:
- Mesothelin is a protein on the lining of the lungs, heart, and abdomen. It is often present at higher levels on some cancer cells. Anticancer drugs given directly to cells with high mesothelin levels may help destroy the cancer cells with fewer effects on healthy cells. BAY 94-9343 combines an anticancer drug with a type of protein that targets mesothelin. Researchers want to see if BAY 94-9343 can treat advanced cancers that have mesothelin on the cells.
- Objectives:
- To test the safety and effectiveness of BAY 94-9343 on advanced solid tumors.
- Eligibility:
- Individuals at least 18 years of age who have advanced solid tumors that have mesothelin on the cells.
- Design:
-
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam will also be included.
- The study drug will be given in 3-week cycles of treatment. At the start of each cycle, participants will have BAY 94-9343 as an infusion for about 1 hour.
- Treatment will be monitored with frequent blood tests, heart and lung function tests, and imaging studies. Treatment will continue as long as the tumor does not start growing and no severe side effects develop.
Study of ABT-700 in Subjects With Advanced Solid Tumors
Purpose: This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-700 in subjects with advanced solid tumors. The early clinical development plan for ABT-700 is based on the activity demonstrated in preclinical models. Approximately 51 to 75 subjects will be enrolled.
- Arms
-
- Cohort A: Experimental
- ABT-700 will be administered by intravenous infusion at escalating dose levels in 21-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-700.
- Intervention: Drug: ABT-700
- Cohort B: Experimental
- ABT-700 plus erlotinib 150 mg qd (21-day cycle).
- Intervention: Drug: ABT-700 plus erlotinib
- Cohort C: Experimental
- ABT-700 plus oxaliplatin and capecitabine. ABT-700 IV (Day 1) Oxaliplatin: 130 mg/m2 IV (Day 1) Capecitabine: 1000 mg/m2 Oral (twice daily Days 1 – 14).
- Intervention: Drug: ABT-700 plus Oxaliplatin and Capecitabine
- Cohort A: Experimental
SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma
Purpose:
- Background:
- Standard therapy for mesothelioma is a combination of the drugs pemetrexed and cisplatin. However, the benefits of this treatment are limited, and in most treated patients the disease continues to worsen.
- SS1(dsFV)PE38 is a genetically engineered drug. It contains an antibody that binds to a certain protein on mesothelioma cells and a toxin (type of poison) made from a product of a bacterium called Pseudomonas aeruginosa. It is hoped that the antibody will attach to the cancer cells, allowing the toxin to enter and kill the cells.
- Objectives:
- To find out if SS1(dsFV)PE38, together with pemetrexed and cisplatin is safe and tolerable in patients with mesothelioma.
- To determine the maximum tolerated dose of SS1(dsFV)PE38 (the highest dose that does not cause unacceptable side effects).
- To see if SS1(dsFV)PE38 given with pemetrexed and cisplatin has any effect on patients’ tumors.
- To learn how the body breaks down SS1(dsFV)PE38.
- Eligibility:
- Patients 18 years of age and older with epithelial pleural mesothelioma whose disease cannot be cured with surgery, and have not had prior treatment with chemotherapy.
- Design:
- Treatment with pemetrexed, cisplatin and SS1(dsFV)PE38 in two 21-day cycles as follows:
-
- Day 1 – Intravenous (through a vein) infusions of pemetrexed and cisplatin.
- Days 1 and 2 – Intravenous solution to prevent dehydration that might occur with SS1(dsFV)PE38.
- Days 1, 3 and 5 – Intravenous infusion of SS1(dsFV)PE38. Small groups (3 to 6) of patients are given SS1(dsFV)PE38 at a certain dose level. If the first group experiences no significant side effects, the next group a higher dose. This continues in succeeding groups until the maximum tolerated study dose (highest dose that patients can be given safely) is determined.
- Continuing standard treatment with additional cycles of pemetrexed and cisplatin.
- Evaluations during the treatment period:
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- Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
- Questions about medications and side effects.
- Blood and urine tests.
- Disease evaluation with CT, chest X-ray, and possibly PET scans, lung function tests, pulse oximetry, performance of daily activities and quality-of-life questionnaires.
- Post-treatment evaluations:
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- Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease assessment.
- End-of-study visit for bl…
