4513 Background: CCI-779 is an mTOR kinase inhibitor with activity in renal cell carcinoma (RCC, Atkins et al. J Clin Oncol, in press). A preliminary report of this phase 1/2 study of CCI-779 and interferon-α (IFN) in patients (pts) with advanced RCC described the safety and antitumor effects of the combination (Dutcher et al. Proc ASCO 22:213, 2003). We update these results. Methods: In an open-label, escalating-dose, single-arm study, CCI-779 was given intravenously once weekly, with IFN given subcutaneously 3 times weekly. The starting dose levels were 6 million units (MU) IFN, 5 mg CCI-779. Dose escalation was based on safety evaluation of pts (≥ 6/cohort) after 4 wks of treatment. Up to 40 pts will be evaluated at the maximum tolerated dose (MTD). Results: As of 01 Dec 2003, 71 pts with advanced RCC were enrolled; 27 continue treatment. Pts (73% men, 27% women) had ECOG performance status of 0: 53% and 1: 46% and median age of 59 yrs (range, 35–80); 45% had prior IL-2 treatment. In dose escalation, pts received 6 MU IFN with CCI-779 at 5 mg (7 pts), 10 mg (6), 15 mg (6), 20 mg (6), or 25 mg (7); 6 pts also received 9 MU IFN with 15 mg CCI-779. Based on dose-limiting toxicities, 15 mg CCI-779, 6 MU IFN was selected as the MTD. To date, 33 additional pts have been accrued at the MTD. Grade 3–4 CCI-779-related adverse events with overall frequency ≥ 5% (n=53) were leukopenia (25%), hyperlipidemia (15%), asthenia (13%), AST increase (8%), mucositis (6%), anemia (6%), thrombocytopenia (6%), and rash (6%). Four pts were removed from study due to CCI-779-related toxicity. Approximately 50% of MTD pts have required CCI-779 dose reductions in subsequent cycles. Median time on treatment for all cohorts was 7 mo, 36 have continued for ≥ 6 mo of whom 9 have continued for > 12 mo. Preliminary tumor responses (RECIST) in 55 pts were confirmed partial response, 7 pts (13%); stable disease, 39 (71%, 19 pts ≥ 6 mo); and progressive disease, 9 (16%). Conclusions: CCI-779 and IFN showed favorable results for safety and efficacy. A phase 3 trial has been initiated that compares this combination of CCI-779 and IFN with each agent alone as first-line therapy in poor-risk pts with metastatic RCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth Research Wyeth Parmaceuticals
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Smith et al. (2004) studied this question.