Sorafenib (SOR) or placebo (PL) in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (SPACE).

Abstract

TPS178^ Background: SOR acts via antiangiogenesis and inhibition of tumor cell proliferation, and has proven efficacy in advanced hepatocellular carcinoma (HCC). It is relevant to assess whether SOR combined with TACE improves clinical outcomes compared with TACE alone. The phase II SPACE study is being conducted in North America, Europe, and the Asia-Pacific region to evaluate the efficacy and safety of TACE (using doxorubicin-eluting beads) plus either SOR or PL in patients (pts) with intermediate-stage HCC (BCLC B). Methods: SPACE is a multinational, randomized, double-blind, PL-controlled study. Pts aged ≥18 years diagnosed with intermediate-stage HCC (BCLC B; defined as the presence of asymptomatic, unresectable, multinodular tumors without vascular invasion or extrahepatic spread) are eligible if they have Child-Pugh (CP) class A status without ascites; ECOG PS of 0; ≥1 unidimensional lesion measurable according to RECIST; and adequate bone marrow, liver, and renal function. Exclusion criteria include diffuse HCC or vascular invasion (including segmental portal obstruction) and/or extrahepatic spread; advanced liver disease (defined as CP class B/C, active gastrointestinal bleeding, and/or encephalopathy); contraindication to TACE; history of a target lesion treated previously with local therapy; any locoregional therapy ongoing or completed <4 weeks prior to baseline; and history of ≥grade 2 adverse event with any prior local treatment. Eligible pts undergoing TACE with doxorubicin-eluting beads (loaded with 150 mg doxorubicin) are randomized 1:1 to SOR 400 mg bid or matching PL orally on a continuous basis. Treatment cycles are repeated every 4 weeks until untreatable progression (defined as failure to achieve objective response after ≥2 TACE in the treated tumor nodule). TACE is performed on day 1 of cycles 1, 3, 7, 13, and every 6 cycles thereafter. All endpoints will be assessed on an ITT basis. The primary study endpoint is time to progression. Secondary endpoints are overall survival, time to untreatable progression, time to vascular invasion/extrahepatic spread, and safety. Estimated overall accrual is 300 subjects. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer, Bristol-Myers Squibb Bayer In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.