Dataset Information

AB046. P-14. TREETOPP: a phase 2/3 study of varlitinib plus capecitabine versus placebo plus capecitabine as second-line treatment in patients with advanced or metastatic biliary tract cancers (BTCs)

ABSTRACT: Background Biliary tract cancers (BTCs) are rare and have a poor prognosis. These cancers are often diagnosed at advanced stage with limited treatment options and poor overall survival (OS). Overexpression of epidermal growth factor receptor (EGFR), HER2, HER3, and HER4 vary from 23–57%, 4–13%, 12–23% and 59–60% of BTCs, respectively. Varlitinib is a small molecular tyrosine kinase inhibitor of EGFR, HER2 and HER4 with potent antitumor effect in preclinical BTC models. Varlitinib also demonstrated tumor shrinkage responses and durable disease stabilization in BTC patients in phase IB study. Methods A randomized, double-blind, placebo-controlled phase 2 (Part 1)/3 (Part 2) study to compare the efficacy of varlitinib (300 mg BID, every day) versus placebo, when combined with capecitabine (1,000 mg/m2, BID for 14 days). The primary endpoints of Part 1 are objective response rate (ORR) and progression-free survival (PFS) and for Part 2 is OS. Eligible patients include those with confirmed advanced or metastatic 2nd line BTC, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of ampulla of Vater. Patients must have failed gemcitabine-contained 1st line systemic treatment. The target sample size is 482 patients, and enrollment has started on May 24, 2017. Safety data will be listed and summarized. Co-primary endpoints of Part 1 will be analyzed using data from an Independent Central Review of radiological data. A Hochberg procedure will be used to control the familywise type I error rate for Part 1 at the 10% level (one-sided). For Part 2, the primary endpoint, OS, will be tested at the two-sided 5% significance level. Trial registration Clinical trial information: NCT03093870

SUBMITTER: Javle M

PROVIDER: S-EPMC6421189 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPatients with advanced biliary tract cancer who progress on first-line therapy have limited treatment options. The TreeTopp study assessed varlitinib, a reversible small molecule pan-human epidermal growth factor receptor inhibitor, plus capecitabine in previously treated advanced biliary tract cancer.Patients and methodsThis global, double-blind, randomized, placebo-controlled phase II study enrolled patients with confirmed unresectable or metastatic biliary tract cancer and disease progression after one prior line of gemcitabine-containing chemotherapy. Patients received oral varlitinib 300 mg or placebo twice daily (b.i.d.) for 21 days, plus oral capecitabine 1000 mg/m2 b.i.d. on days 1-14, in 21-day treatment cycles. Co-primary endpoints were objective response rate and progression-free survival (PFS) according to RECIST v1.1 by Independent Central Review.ResultsIn total, 127 patients received varlitinib plus capecitabine (n = 64) or placebo plus capecitabine (n = 63). The objective response rate was 9.4% with varlitinib plus capecitabine versus 4.8% with capecitabine alone (odds ratio 2.28; P = 0.42). Median PFS was 2.83 versus 2.79 months [hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.60-1.37; P = 0.63] and overall survival was 7.8 versus 7.5 months (HR, 1.11; 95% CI, 0.69-1.79; P = 0.66), respectively. In a subgroup analysis, the addition of varlitinib appeared to provide a PFS benefit in female patients (median, 4.1 versus 2.8 months; HR, 0.59; 95% CI, 0.28-1.23) and those with gallbladder cancer (median, 2.9 versus 1.6 months; HR, 0.55; 95% CI, 0.26-1.19). Grade ≥3 treatment-emergent adverse events were reported in 65.6% of patients receiving varlitinib plus capecitabine versus 58.7% of those receiving capecitabine alone.ConclusionsIn patients with advanced biliary tract cancer, second-line treatment with varlitinib plus capecitabine was well tolerated but did not improve efficacy versus capecitabine alone. A PFS benefit was suggested in female patients and those with gallbladder cancer.

Project description:Background & aimsGallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.MethodsWe pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.ResultsDuring 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.ConclusionWe observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.Lay summaryOur findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Dataset Information

AB046. P-14. TREETOPP: a phase 2/3 study of varlitinib plus capecitabine versus placebo plus capecitabine as second-line treatment in patients with advanced or metastatic biliary tract cancers (BTCs)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets