Earlier this month recruitment has begun to enroll patients in an international Phase III trial to evaluate sorafenib (Nexavar?) tablets for the treatment of patients with radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer (papillary, follicular and Hurthle cell). The study is scheduled to start later this month at sites in the United States, Europe, Asia, and Japan. The study is schedules to complete in November 2011.Thyroid cancer, one of the few cancers that has increased in incidence over the past several years. According to the American Cancer Society, it is the sixth most common cancer and about three times as many women as men get thyroid cancer. Information from the World Health Organization (Globocan 2002 database) indicates that there are more than 140,000 new cases of thyroid cancer and more than 35,000 people die worldwide each year.”Patients with thyroid cancer who failed to respond to surgical or radiotherapies, have limited treatment options to help them manage their disease,” said Dimitris Voliotis, vice president, Nexavar clinical development, Bayer HealthCare Pharmaceuticals. “Recognizing this unmet need, we are evaluating Nexavar in this special patient population.”Phase III Trial DesignThe DECISION (stuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine refractory thyrOid caNcer) trial is an international, multicenter, randomized, placebo-controlled study that will enroll approximately 400 patients with locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer (papillary, follicular and Hurthle cell) who have received no prior systemic therapy.Patients will be randomized to receive 400 mg of oral sorafenib twice daily or matching placebo. Patients will continue on treatment until disease progression, toxicity, non-compliance or withdrawal of consent. At the time of progression, patients receiving placebo will have an option to cross over to sorafenib at the discretion of the investigator, based on the patient’s clinical status. The primary endpoint of the study is progression-free survival as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints include overall survival, time to progression and response rate. The safety and tolerability of the two treatment groups will also be compared.Phase II Trial ResultsThis Phase III trial initiative was started based on the results from Phase II clinical trials evaluating sorafenib in patients with advanced thyroid cancer.Updated results from a single institution, investigator sponsored Phase II open-label study in 55 patients with metastatic, iodine refractory, thyroid cancer treated with Sorafenib r 400 mg twice daily were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 29-June 3, 2009 Orlando, FL, by Marcia Brose, M.D., Ph.D., an assistant professor of Hematology/Oncology and Otorhinolaryngology in the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, U.S.A. In 50 evaluable patients, 18 (36%) had a partial response per RECIST criteria.The survival results on the first 30 patients enrolled into the study demonstrated that across all histologies the median progression-free survival (PFS) was 63 weeks and the median overall survival was 140 weeks. The most common adverse events (AE) seen in the trial were hand-foot skin reaction, rash, fatigue, stomatitis/mucositis, weight loss, and musculoskeletal pain, and were predominantly grade 1 or 2. Dr. Brose and Martin J. Schlumberger, Institut Gustave-Roussy, Villejuif, France, are the lead investigators on the Phase III trial.”Based on the positive signal generated in the Phase II trial, the initiation of this Phase III represents progress in exploring the full potential of Nexavar in a variety of treatment settings and tumor types,” noted Todd Yancey, M.D., vice president of clinical development at Onyx. “Building on our successful foundation of treating unresectable liver cancer and advanced kidney cancer, we are hopeful that this Phase III trial will lead to a new treatment option for patients with non-responsive thyroid cancer.”A Differentiated Mechanism of ActionSorafenib is one of the first of a new class of drugs. In preclinical studies, the drug has shown to block a variety of multiple kinases. Multiple kinase inhibition works at multiple levels of signaling pathways in tumor cells and tumor vasculature – important processes that enable cancer growth. These targets include Raf kinase, VEGFR-1, 2 and 3 (Vascular Endothelial Growth Factor Receptor), PDGFR-B (Platelet Derived Growth Factor Receptor), KIT, FLT-3 and RET.Sorafenib is currently approved in more than 80 countries for the treatment of patients with hepatocellular carcinoma (HCC), or liver cancer, and in more than 90 countries for the treatment of patients with advanced renal cell carcinoma (RCC), or kidney cancer. Even though these indications are well established, the utility of sorafenib continues to be evaluated in these tumor types, with ongoing studies examining special patient populations and long-term use.Data on these indications was presented at Europe?s largest cancer congress, the ECCO 15 ? ESMO 34 meeting in Berlin (Germany) and included results from two Phase III studies evaluating sorafenib in HCC and six studies examining sorafenib in RCC. During the same meeting, phase II study data of single-agent sorafenib in patients with thyroid cancer was also presented (Late-breaking poster 51LBA, Poster 276, Tuesday, September 22, 9:00 a.m.-5:00 p.m. Hall 14.1)Ongoing trialsIn addition to its current indications, sorafenib continues to be evaluated as a single agent or combination treatment in a wide range of cancers, including breast cancer and as an adjuvant therapy for kidney cancer and liver cancer.Data from a recently unblinded Phase II trial evaluating the safety and efficacy of Nexavar as a potential treatment for breast cancer will be presented during an oral session at ECCO-ESMO. This trial examined sorafenib compared to placebo in combination with the oral chemotherapeutic agent, capecitabine, in patients with locally advanced or metastatic breast cancer. (Late-breaking presentation 3LBA, Presidential Session III, Wednesday, September 23, 1:30 p.m., Hall 1)Sorafenib is also being evaluated as a single agent or combination treatment in a wide range of cancers, including breast cancer, colorectal cancer, lung cancer, ovarian cancer, and as an adjuvant therapy for liver cancer.Sorafenib (Nexavar?) is being co-developed by Bayer HealthCare AG and Onyx Pharmaceuticals, Inc.

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