SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma


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.
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.
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.
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:
  • 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:
  • Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease assessment.
  • End-of-study visit for bl…

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Amatuximab for High Mesothelin Cancers


Amatuximab is a cancer treatment drug that targets mesothelin. High levels of this substance are found on some kinds of tumor cells. Lab studies have shown that amatuximab helps the immune system to kill cells that have high levels of mesothelin. However, more research is needed to determine how safe and effective amatuximab is for treating tumors with high levels of mesothelin.
To assess the safety and effectiveness of amatuximab in treating tumors with high levels of mesothelin.
Individuals at least 18 years of age who have a type of cancer that overexpresses mesothelin.
  • Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor assessment studies.
  • Participants will have two intravenous doses of amatuximab several hours apart. Researchers will monitor them closely and do frequent blood draws. On the same day and also within 48 hours of the second dose, participants will have imaging studies. These studies will measure how well the amatuximab is working against the cancer.
  • Participants will have a third imaging study of the cancer about 1 week after the infusions.
  • Participants will have a followup visit 2 weeks after receiving amatuximab. This visit will require blood samples. Four weeks after receiving the drug, researchers will review patients’ symptoms or side effects. This interview can be done in person or by phone….

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Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome

Rationale: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with pemetrexed disodium may kill more cancer cells.

Purpose: This phase I/II trial is studying the side effects and best dose of gemcitabine hydrochloride when given together with pemetrexed disodium and to see how well they work in treating patients with advanced mycosis fungoides or Sézary syndrome.

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Pulmonary Interstitial Lymphography in Early Stage Lung Cancer

Purpose: Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world. NSCLC annually causes 150,000 deaths in the US and greater than 1 million worldwide. The standard treatment for early stage NSCLC is lobectomy with lymphadenectomy. However, many patients are poor operative candidates or decline surgery. An emerging alternative is Stereotactic Body Radiation Therapy (SBRT). Mounting evidence from Phase I/II studies demonstrates that SBRT offers excellent local control. Most SBRT trials focused on small, peripheral tumors in inoperable patients. Increasingly, clinical trials study SBRT in operable patients, often with larger, central tumors.

Using clinical staging, a significant proportion of patients harbor occult nodal metastases when undergoing SBRT to the primary tumor alone. Subgroups of patients carry even higher risk of nodal metastases. These nodal metastases frequently would be removed by surgical intervention. However, SBRT, at present, is only directed at the primary tumor, potentially leading to regional failures in otherwise curable patients. To increase the effectiveness of SBRT for lung tumors, the next logical step is to explore whether the highest risk areas of disease spread can be identified and targeted. Regional failure could be reduced and outcome improved in a significant proportion of patients treated with SBRT if the primary nodal drainage (PND) were identified, targeted and treated in addition to the primary tumor.

We propose to conduct a study to determine how well water soluble iodinated contrast material when injected directly into the tumor can be visualized on CT scan and integrated into radiation therapy treatment planning.

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Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

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.

To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.
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.
  • 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.

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Immunotoxin Therapy, Pemetrexed, and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed by Surgery

Rationale: Immunotoxins can find tumor cells and kill them without harming normal cells. Drugs used in chemotherapy, such as pemetrexed 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 more than one drug (combination chemotherapy) together with immunotoxin therapy may kill more malignant mesothelioma cells.

Purpose: This phase I trial is studying the side effects and best dose of immunotoxin therapy when given together with pemetrexed and cisplatin in treating patients with malignant pleural mesothelioma that cannot be removed by surgery.

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Depsipeptide/Flavopiridol Infusion for Cancers of the Lungs, Esophagus, Pleura, Thymus or Mediastinum

Purpose: This study will test the safety and effectiveness of two experimental medicines – depsipeptide and flavopiridol – given together to treat cancers of the lung, esophagus, and pleura. It will determine the highest dose that these drugs can safely be given together and will test whether giving them together works better at shrinking tumors than giving either one alone.

Patients 18 years of age and older with cancer of the lung, esophagus, or pleura, or other cancers that have spread to the lungs or pleura may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), x-rays and scans, pulmonary function tests, and a tumor biopsy (removal of a small piece of tumor tissue for microscopic examination).

Participants are admitted to the hospital for treatment for approximately 10 days during each 28-day treatment cycle. Depsipeptide is infused through an arm vein or central venous catheter (tube placed in a large vein in the neck or chest) for 4 hours. When this infusion is complete, flavopiridol is infused over 72 hours. The dose of depsipeptide is increased four times over the period of the study with successive groups of patients, and flavopiridol is increased once to determine the maximum safe dose of giving these drugs together.

Blood tests are done before and after each depsipeptide infusion and 3 more times for the next 24 hours, and at various times over 4 days during the flavopiridol infusion to evaluate the effects of the medicines. Samples are also drawn periodically throughout the treatment cycle to evaluate safety. Heart function is monitored with several EKGs before and during the depsipeptide doses. The drug has shown effects on EKG tracings, but does not appear to injure the heart muscle.

Tumor biopsies are done before treatment begins and on the fifth day of the first treatment cycle. The biopsies may be done either in the operating room by passing a tube (bronchoscope) down the throat and into the lungs or in the Radiology Department using a thin needle put through the chest wall into the tumor. For the bronchoscopy, numbing medicine is sprayed into the back of the throat to reduce discomfort, and for the needle biopsy, the skin over the biopsy area is numbed. Optional repeat biopsies may be requested before the start of the second treatment cycle and on day 5 of that cycle. (The repeat biopsies are not required for participation in the study.) At the time of each tumor biopsy, a buccal mucosal biopsy is also done. This involves scraping a tongue depressor along the inside of the mouth to collect cells for examination.

At the end of the first treatment cycle, patients return to NIH for evaluation with a physical examination, blood work, x-rays, and scans of the chest, abdomen, pelvis, and brain. Patients who are not experiencing significant drug side effects are offered a second cycle, exactly like the first. The two cycles complete one course of treatment, after which patients once again return to NIH for evaluation. Additional treatment cycles may be offered to patients whose tumors have shrunk or remained stable with therapy. Patients whose tumors have not responded to therapy or who have developed severe drug side effects are taken off the study.

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