A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

Summary

Background: * Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses. * YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments. Objectives: \- To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer. Eligibility: \- Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective. Design: * Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors. * Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required. * On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump). * Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site. * After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.

Timeline

Start

2010-02

Primary completion

2012-12

Completion

2012-12

Publications

• Background Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
• Background Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.
• Background Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR; American Society of Clinical Oncology. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol. 2004 Jan 15;22(2):330-53. doi: 10.1200/JCO.2004.09.053. Epub 2003 Dec 22. No abstract available.
• Kelly RJ, Thomas A, Rajan A, Chun G, Lopez-Chavez A, Szabo E, Spencer S, Carter CA, Guha U, Khozin S, Poondru S, Van Sant C, Keating A, Steinberg SM, Figg W, Giaccone G. A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013 Oct;24(10):2601-2606. doi: 10.1093/annonc/mdt249. Epub 2013 Jul 14.

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Indications