CAT-5001

Background:
Advanced cases of non-small-cell lung carcinoma (NSCLC) usually are not successfully treated with standard therapies. Even treatments that attempt to specifically target NSCLC cells have not proved effective.
Researchers are interested in determining whether a combination of the chemotherapy drugs SS1 (dsFv) PE38, paclitaxel, carboplatin, and bevacizumab may be effective in shrinking the size of NSCLC tumors. Three of the drugs (paclitaxel, carboplatin, and bevacizumab) are commercially available, while the other is a drug that is currently being tested to determine its usefulness in cancer treatment. This study will help to determine if the combination of all four drugs is more effective and as safe, safer, or less safe than other drug combinations given to treat NSCLC.
Objectives:
- To determine a safe and tolerable dose for the combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin, and bevacizumab in patients with advanced mesothelin-expressing lung adenocarcinoma.
Eligibility:
Age > 18 years of age
Newly diagnosed advanced non-small-cell lung carcinoma
No prior chemotherapy for lung cancer
Individuals at least 18 years of age who have advanced non-small-cell lung carcinoma that has not responded to standard treatments.
Design:
The study will last for two 21-day cycles of treatment for the four-drug combination, with additional treatment cycles of carboplatin, paclitaxel, and bevacizumab.
Two to three weeks prior to the study, participants will be screened with a full medical history and physical exam, bone marrow biopsy (we do not do bone marrow biopsies) (if one has not been performed in the last 6 months), computed tomography (CT) or ultrasound scan, tumor measurements, and other tests as required by the researchers. Participants will provide blood and urine samples at this time as well.
During the study, participants will receive SS1 (dsFv) PE38, carboplatin, paclitaxel, and bevacizumab for a maximum of two cycles. On Day 15 of the first cycle, participants will provide a blood sample to be tested to see if SS1 (dsFv) PE38 is being effective. If the tests show that SS1 (dsFv) PE38 is not effective, participants will not receive another dose of it, but will continue to receive paclitaxel, carboplatin, and bevacizumab for the second cycle.
After the first two cycles, participants will continue to receive carboplatin, paclitaxel, and bevacizumab every 3 weeks for up t...

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:
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 blood tests, vital signs and weight measurements, disease assessment, electrocardiogram, pregnancy test for women who can become pregnant