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
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
- 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.
- Clinic visits at months 1, 3, 6, 12, 15, 18 and 21 for physical examination and disease
- End-of-study visit for blood tests, vital signs and weight measurements, disease
assessment, electrocardiogram, pregnancy test for women who can become pregnant
Study Type: Interventional
Study Design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Official Title: 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
SS1(dsFV)PE38, is a recombinant immunotoxin targeting the tumor antigen mesothelin that is
highly expressed in malignant mesothelioma. The maximum tolerated dose (MTD) of
SS1(dsFV)PE38 has been established in a phase I study.
Combination therapy with pemetrexed plus cisplatin is the standard first line therapy for
malignant mesothelioma, but results in a median overall survival of only 12.1 months.
Combination of SS1(dsFV)PE38 with pemetrexed plus cisplatin could result in improved
outcomes for patients with mesothelioma.
To determine the MTD of SS1(dsFV)PE38 that can be safely administered in combination with
pemetrexed plus cisplatin in patients with mesothelioma.
To characterize the toxicity profile of SS1(dsFV)PE38.
To study the pharmacokinetics of SS1(dsFV)PE388.
To observe anti-tumor activity, if any of SS1(dsFV)PE38 in combination with pemetrexed plus
Subjects with histologically confirmed epithelial pleural mesothelioma.
No prior radiotherapy (except palliative extra-thoracic localized radiotherapy),systemic
chemotherapy or biologic therapy for pleural mesothelioma.
This is a phase I dose-escalation study of SS1(dsFV)PE38 in combination with pemetrexed plus
The dose of pemetrexed plus cisplatin will be the standard dose approved for malignant
mesothelioma. The dose of SS1(dsFV)PE38 will be escalated to find the safe dose in
combination with pemetrexed plus cisplatin.
SS1(dsFV)PE38 will be administered concurrently with pemetrexed plus cisplatin in cycles one
and two, and subjects will receive additional cycles of pemetrexed and cisplatin as per
Patients will be assessed for response every 6 weeks.
An additional Single Cycle of SS1(dsFv)PE38 Cohort will involve up to 16 patients who
will receive SS1(dsFv)PE38 administered for four or five doses during the first cycle
concurrently with pemetrexed and cisplatin; subjects in this cohort will receive additional
cycles of pemetrexed and cisplatin as per standard practice
Enrollment Size: Both
Gender: 18 Years
Min. Age: N/A
Max. Age: No
Location and Contact Information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland, 20892, United States
Last modified: May 22, 2015.