A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma
- 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.
- 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.
- 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.
- 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...
Non-Small Cell Lung Cancer
Drug: SS1 (dsFv) PE38
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma|
- Determined safe and tolerable phase 2 dose for combination of SS1 (dsFv) PE38 with paclitaxel, carboplatin, and bevacizumab.
- Study pharmacokinetics. Assess response rate, duration of response and progression-free survival.
|Study Start Date:||December 2009|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
Drug: SS1 (dsFv) PE38
- 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.
- 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.
- 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.
- 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.
- Open label phase I trial.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|