Eng, Charis

Abstract Background: Research biobanks collect biologic samples and health information. Previous work shows that biobank participants desire general study updates, but preferences about the method or frequency of these communications have not been explored. Thus, we surveyed participants in a long-standing research biobank. Methods: Eligible participants were drawn from a study of patients with personal/family history suggestive of Cowden syndrome, a poorly recognized inherited cancer syndrome. Participants gave blood samples and access to medical records and received individual results but had no other study interactions. The biobank had 3,618 participants at sampling. Survey eligibility included age ≥18 years, enrollment within the biobank's first 5 years, normal PTEN analysis, and contiguous U.S. address. Multivariate logistic regression analyses identified predictors of participant interest in Internet-based versus offline methods and methods allowing participant–researcher interaction versus one-way communication. Independent variables were narrowed by independent Pearson correlations by cutoff P < 0.2, with P < 0.02 considered significant. Results: Surveys were returned from 840 of 1,267 (66%) eligible subjects. Most (97%) wanted study updates, with 92% wanting updates at least once a year. Participants preferred paper (66%) or emailed (62%) newsletter methods, with 95% selecting one of these. Older, less-educated, and lower-income respondents strongly preferred offline approaches (P < 0.001). Most (93%) had no concerns about receiving updates and 97% were willing to provide health updates to researchers. Conclusion: Most participants were comfortable receiving and providing updated information. Demographic factors predicted communication preferences. Impact: Researchers should make plans for ongoing communication early in study development and funders should support the necessary infrastructure for these efforts. Cancer Epidemiol Biomarkers Prev; 24(4); 708–12. ©2015 AACR.

Abstract A hypoxic microenvironment is believed to be a characteristic of solid tumors including pancreatic adenocarcinoma (PAC) and is associated with resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to specifically target the hypoxic microenvironment. Combining G with TH-302 may enable the targeting of both the normoxic and hypoxic regions of PAC. TH-302 was investigated with full-dose G as part of a Phase 1/2 study with a 21% response, median PFS and OS of 5.9 and 8.5 months, respectively, and one-year survival of >40%. Based upon these data, a randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G+T to standard dose G for first-line therapy of PAC. An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1) was initiated in June 2010. G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G arm could crossover after progression and be randomized to a G+T arm. The primary efficacy endpoint is a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). 214 pts (69 G: 71 G+T240: 74 G+T340) with advanced PAC including 77% distant metastases, 62% involving liver and 11% with prior adjuvant tx; median age: 65 (range 29-86); 126 M/88 F; 79/128 ECOG 0/1. Median cycles received: G - 4, G+T240 - 5, G+T340 - 6. Median PFS was 3.6 mo in G vs 5.6 mo in G+T arms with HR of 0.61 (95% CI: 0.43 - 0.87) and logrank p-value of 0.005. Median PFS in G + T340 was 6.0 mo. RECIST best response was 12% in G, 17% in G+T 240 and 27% in G+T340. 153 (71%) patients had elevated CA19-9 and follow-up. CA19-9 decreases were significantly greater in the G+T groups and greatest in the G+T340 arm which had 37 of 53 (70%) pts with a greater than 50% CA19-9 decrease. One death (suicide) was considered possibly related to study drug. Adverse events leading to discontinuation were: 16% G, 15% G+T240 and 11% G+T340. Serious adverse events were balanced across the treatment arms. The most common non-laboratory events, fatigue (49%), nausea (43%), constipation (34%) and peripheral edema (38%), were similar across groups. Rash (14% G, 39% G+T240 and 45% G+T340) and stomatitis (6% G, 17% G+T240 and 36% G+T340) were significantly greater with G+T combination but no Grd 4 (4 pts with Grade 3). Grd 3/4 thrombocytopenia (11% G, 39% G+T240 and 59% G+T340) and Grd 3/4 neutropenia (28% G, 56% G+T240 and 59% G+T340) were higher with G+T. G+T combination with full dose G improved the efficacy of G with significantly longer PFS, higher response rate and greater CA19-9 declines. The G+T combination was well tolerated. Skin and mucosal toxicity and myelosuppression were the most common related adverse events with no increase in treatment discontinuation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-121. doi:1538-7445.AM2012-LB-121