A Phase 1, Single Center, Dose-Escalation Study of SS1(dsFv)PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma

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