SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma

Summary

Background: * Malignant mesothelioma is a form of cancer that develops on the protective lining that covers the body's internal organs. It most often occurs on the lining of the lungs and chest wall or the lining of the abdomen. There is no known cure for malignant mesothelioma, so researchers are searching for new ways to treat it. * Mesothelin is a protein that is found in mesothelioma and other types of cancer cells. An experimental cancer drug called SS1P is designed to attack cells that have mesothelin while leaving healthy cells alone. Researchers want to test how effective SS1P is when it is given with pentostatin and cyclophosphamide. These drugs help suppress the immune system and may make the SS1P more effective. Objectives: \- To study the effectiveness of SS1P plus two drugs that suppress the immune system to treat malignant mesothelioma. Eligibility: \- Individuals at least 18 years of age who have malignant mesothelioma in the chest or abdomen. Design: * Participants will be screened with a physical exam, medical history, and blood tests. They will also have imaging studies. * The first treatment cycle will last 30 days. Up to three 21-day cycles of treatment will follow. * In the first cycle, participants will have pentostatin on days 1, 5, and 9. They will have cyclophosphamide on days 1 through 12. They will have SS1P on days 10, 12, and 14. * On the next three cycles, participants will have pentostatin on day 1.They will have cyclophosphamide on days 1 through 4. They will have SS1P on days 2, 4, and 6. * Participants will have frequent blood tests and other studies. They will receive all four cycles of treatment as long as there are no severe side effects. * Participants will have regular followup visits as directed by the study doctors.

Timeline

Start

2011-05-11

Primary completion

2016-08-03

Completion

2017-08-07

Publications

• Background Hassan R, Bullock S, Premkumar A, Kreitman RJ, Kindler H, Willingham MC, Pastan I. Phase I study of SS1P, a recombinant anti-mesothelin immunotoxin given as a bolus I.V. infusion to patients with mesothelin-expressing mesothelioma, ovarian, and pancreatic cancers. Clin Cancer Res. 2007 Sep 1;13(17):5144-9. doi: 10.1158/1078-0432.CCR-07-0869.
• Background Kay NE, Geyer SM, Call TG, Shanafelt TD, Zent CS, Jelinek DF, Tschumper R, Bone ND, Dewald GW, Lin TS, Heerema NA, Smith L, Grever MR, Byrd JC. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood. 2007 Jan 15;109(2):405-11. doi: 10.1182/blood-2006-07-033274. Epub 2006 Sep 28.
• Background Zhang Y, Xiang L, Hassan R, Paik CH, Carrasquillo JA, Jang BS, Le N, Ho M, Pastan I. Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice. Clin Cancer Res. 2006 Aug 1;12(15):4695-701. doi: 10.1158/1078-0432.CCR-06-0346.

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Indications