A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma
- Treatment with platinum-based doublet chemotherapy results in a median survival of 7 to
10 months in patients with locally advanced or metastatic non-small cell lung cancer.
- In a randomized clinical trial of patients with non-squamous cell lung cancer,
treatment with carboplatin, paclitaxel and bevacizumab resulted in an objective
response rate of 35%, overall survival of 12.3 months compared to objective response
rate of 15%, overall survival of 10.3 months in patients treated with carboplatin and
paclitaxel alone.
- Mesothelin is a cell surface glycoprotein present on normal mesothelial cells that is
highly expressed in many human cancers including lung adenocarcinoma.
- SS1 (dsFv) PE38 is a recombinant anti-mesothelin immunotoxin that has undergone phase I
testing and is currently in clinical trials in combination with pemetrexed and
cisplatin for treatment of malignant pleural mesothelioma.
- Pre-clinical studies demonstrate increased anti-tumor activity of SS1 (dsFv) PE38 in
combination with chemotherapy and bevacizumab against mesothelin-expressing tumors.
Primary Objectives:
- This is a phase I study to determine a safe and tolerable phase II dose for the
combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin and bevacizumab in patients with
advanced mesothelin-expressing lung adenocarcinoma.
Secondary Objectives:
- To assess response rate, duration of response, and progression-free survival (PFS).
- To characterize the pharmacokinetics (PK) of SS1 (dsFv) PE38 in combination with
chemotherapy and bevacizumab.
- Monitor serum mesothelin levels prior to and during chemotherapy.
- To identify T-cell epitopes responsible for neutralizing SS1 (dsFv) PE38 activity using
mononuclear cells obtained by apheresis.
Eligibility:
- Histologically confirmed stage IIIB (malignant pleural effusion) or IV or recurrent
NSCLC (non-squamous cell, with mesothelin expression greater than or equal to 10% of
tumor cells by IHC).
- Adequate organ and bone marrow function.
- ECOG performance status of 0-1.
Design:
- Open label phase I trial.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determined safe and tolerable phase 2 dose for combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin, and bevacizumab.
United States: Federal Government
100032
NCT01051934
December 2009
September 2011
Name | Location |
---|---|
National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |