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A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

ABSTRACT: BACKGROUND:Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC. METHODS:All patients were required to have a Karnofsky Performance Status >?70% and adequate organ function. The phase Ib dose escalation cohort included patients with advanced solid tumors who had progressed on all standard therapies. Using a standard 3?+?3 design, we identified the MTD and RPTD for the combination. Fifty patients with metastatic CRC who had progressed on or were intolerant of a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab were then enrolled in a single-arm phase II expansion cohort, and were treated at the RPTD. Prior EGFR antibody therapy was required for subjects with RAS wildtype tumors. The primary endpoint for the expansion cohort was progression-free survival (PFS) at two months. Secondary endpoints included objective response rate (ORR) and overall survival (OS). RESULTS:A total of 63 patients were enrolled and evaluable for toxicity (13 dose escalation; 50 expansion). The MTD and RPTD were: capecitabine 850?mg/m2, P.O. bid, days 1-14, and ziv-aflibercept 6?mg/kg I.V., day 1, of each 21-day?cycle. In the expansion cohort, 72% of patients were progression-free at two months (95% confidence interval [CI], 60-84%). Median PFS and OS were 3.9?months (95% CI, 2.3-4.5) and 7.1?months (95% CI: 5.8-10.0), respectively. Among all patients evaluable for toxicity, the most common treatment related adverse events (all grade [%]; grade???3 [%]) included palmar-plantar erythrodysesthesia (41%; 6%), hypertension (33%; 22%), and mucositis (19%; 5%). RNA was isolated from archived tumor specimens and gene expression analyses revealed no association between angiogenic biomarkers and clinical outcomes. CONCLUSION:The combination of capecitabine and ziv-aflibercept at the RPTD demonstrated acceptable safety and tolerability. PFS at 2?months in patients with chemotherapy refractory metastatic CRC was significantly greater than that in historical controls, indicating that this combination warrants further study. TRIAL REGISTRATION:This clinical trial was registered in the www.clinicaltrials.gov system as NCT01661972 on July 31, 2012.

SUBMITTER: Strickler JH

PROVIDER: S-EPMC6824108 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

Strickler John H JH Rushing Christel N CN Niedzwiecki Donna D McLeod Abigail A Altomare Ivy I Uronis Hope E HE Hsu S David SD Zafar S Yousuf SY Morse Michael A MA Chang David Z DZ Wells James L JL Blackwell Kimberly L KL Marcom P Kelly PK Arrowood Christy C Bolch Emily E Haley Sherri S Rangwala Fatima A FA Hatch Ace J AJ Nixon Andrew B AB Hurwitz Herbert I HI

BMC cancer 20191101 1

<h4>Background</h4>Patients with chemotherapy refractory metastatic colorectal cancer (CRC) have a poor prognosis and limited therapeutic options. In this phase Ib/II clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RPTD) for the combination of capecitabine and ziv-aflibercept, and then we evaluated the efficacy of the combination in patients with chemotherapy refractory metastatic CRC.<h4>Methods</h4>All patients were required to have a Karnofsky Pe ...[more]

PMID: 31675952

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Project description:BACKGROUND:Myopic choroidal neovascularization (CNV) is the most common sight-threatening complication associated with high myopia. The present study evaluated the efficacy and safety of the intravitreal injection of ziv-aflibercept in patients with myopic CNV. METHODS:This prospective interventional study was conducted on 20 eyes of 20 patients with active myopic CNV. Twelve patients were 40?years or older. This study was performed in the Ophthalmology Department of Tanta University Eye Hospital, Tanta University, Egypt. Optical coherence tomography (OCT) was performed for all patients at baseline and monthly after injection during the 6-month follow up period. The main outcome measures were changes in BCVA and CMT. The exploratory outcome measures were CNV size, IOP and the number of injections needed in each age group during the study period. RESULTS:Patients with myopic CNV younger than 40?years needed fewer injections (2.00?±?0.76) than patients older than 40?years (2.50?±?1.00), with no statistical significance detected between the two groups (p-value 0.246). CNV was smaller in the younger age group (p-value 0.209), best corrected visual acuity (BCVA) improved significantly in the younger and older age groups (p-values 0.001 and 0.028, respectively), and central macular thickness (CMT) decreased significantly after 6?months, from 242.88?±?23.83??m to 191.13?±?13.83??m in the younger age group and from 251.33?±?26.60??m to 197.08?±?17.64??m in the older age group (p =?0.001). No significant correlation was found between the final BCVA and either the spherical equivalent or central macular thickness after 6?months, with p-values of 0.135 and 0.145, respectively. No significant changes in IOP were detected in either group after the intravitreal injection. CONCLUSION:Ziv-aflibercept is a highly effective and safe drug in cases of active myopic CNV; however, a larger number of patients and a longer follow-up period are needed to confirm our results. This study was retrospectively registered at clinicaltrials.gov (ID: NCT04290195) on 26-2-2020.

Dataset Information

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

Publications

A phase Ib study of capecitabine and ziv-aflibercept followed by a phase II single-arm expansion cohort in chemotherapy refractory metastatic colorectal cancer.

Similar Datasets

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