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CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.

e16075 Background: Inhibitors of mTOR improve progression-free survival (PFS) in advanced RCC. We hypothesized that co-administration of the mTOR inhibitor E with an upstream receptor tyrosine kinase inhibitor could augment activity in advanced RCC. We chose to study IM due to its inhibition of PDGFR, a relevant target for RCC with potential activity at both the tumor cell and the pericyte. Methods: Eligible patients had metastatic or unresectable clear cell renal carcinoma, at least one prior systemic therapy, no prior mTOR inhibitor therapy, performance status 0–2, and measurable disease. Treatment consisted of E 2.5 mg p.o. daily and IM 600 mg p.o. daily, a dose determined from a phase I study in GIST. A two-stage design was employed to test for a 3-month PFS of ≥ 70% vs. ≤ 50%. Results: 19 subjects were evaluable for toxicity and 18 for response. Median age 65; number of prior systemic therapies 1:2:3+ (47%:32%:21%); prior sorafenib and/or sunitinib 89%; MSKCC prognostic categories favorable:intermediate:poor (42%:47%:11%). There were no objective responses. Best response was stable disease (67%) and progressive disease (33%). The 3-month PFS rate was 49% (95% C.I. 23%, 72%). The median PFS was 2.9 months (95% C.I. 1.9, 6.2) and the median overall survival was 14.4 months (95% C.I. 11.3, N.R.). Toxicities and lab abnormalities affecting >50% of subjects were: nausea, elevated creatinine, edema, anemia, hypocalcemia, fatigue, diarrhea, vomiting, and dyspnea, and leucopenia. Most common grade 3+ events were: fatigue (16%), pleural effusion (16%), edema (11%), and renal failure (11%). The study was closed after the first stage as the 3-month PFS did not meet continuation criteria. Conclusions: The combination of E 2.5 mg with IM 600 mg in previously-treated patients with advanced RCC did not meet the study-defined level of activity to warrant further investigation. The natural history assumptions for this pretreated RCC population may have been overly optimistic. While the observed PFS is comparable to that reported with E 10mg monotherapy, there appears to be no advantage to combination IM therapy and the incidence of adverse events is high. Further development of this regimen for RCC is not recommended. [Table: see text]

15600 Background: The serine-threonine kinase mTOR is a valid target for RCC therapy with temsirolimus treatment resulting in improved overall survival in poor-risk patients (Hudes G et al., ASCO 2006). RAD001 is an oral inhibitor of mTOR which has demonstrated activity in RCC at 10mg/day (Amato R et al., ASCO 2006). IM is a tyrosine kinase inhibitor (TKI) of platelet-derived growth factor receptor (PDGFR), a target that may promote angiogenesis and growth of RCC. Combined mTOR and PDGFR inhibition with RAD001 and IM may achieve vertical blockade through the PI3K/AKT pathway. Methods: Eligibility: metastatic clear cell RCC, performance status (PS) 0–2, adequate organ function, and prior treatment with = 1 systemic therapy. Doses were based on a phase I study of the combination in GIST (Van Oosterom AT et al., ASCO 2005): RAD001 2.5 mg p.o. daily and IM 600 mg p.o. daily. Patients were reimaged every 6 weeks. This is a 2-stage phase II study to determine the 3-month progression-free rate. Results: 14 pts have been enrolled. Median age 66 years (51–79). 6 pts PS 0 and 8 pts PS 1. Median number of prior therapies 1.5 (1–4). 12 of 14 patients had prior TKI therapy. Prior therapies included sorafenib (11 pts), interferon (7), sunitinib (3), bevacizumab (2), erlotinib (1), panitumumab (1), high-dose IL-2 (1). Of 10 pts evaluable for the primary endpoint, 3 are progression-free = 3 months. Best response for 9 pts evaluable by RECIST: PR/CR 0, SD 7, PD 2. Most common adverse events in 11 evaluable patients include nausea (8), edema (7), increased creatinine (7), fatigue (7), transaminase elevation (6), thrombocytopenia (5), leukopenia (5), cough (5), diarrhea (5). Grade 3 adverse events include fatigue (3), LE edema, rash, pleural effusion, increased creatinine, abdominal pain, and thrombocytopenia (1 each). There were no grade 4 toxicities. Unique suspected RAD001 toxicities include grade 3 pneumonitis (1) and angioedema (1). Conclusions: The combination of RAD001 and IM has moderate toxicity. This is one of the first studies in RCC patients predominantly pretreated with a TKI. 3 month progression-free rate appears to be a clinically relevant endpoint in this population. [Table: see text]