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
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Est MTD, study pharmacokinetics, observe anti-tumor response
Raffit Hassan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|University of Chicago Medical Center||Chicago, Illinois 60637|