X-TRAP: Phase I/II study of capecitabine (X) plus ziv-aflibercept (TRAP) in metastatic colorectal cancer (mCRC).
687 Background: Patients (pts) with chemotherapy refractory mCRC have a poor prognosis, with a median survival of approximately 6 months (mos). Ziv-aflibercept is FDA-approved in combination with FOLFIRI for the 2nd line treatment of mCRC, but its tolerability and activity in pts with chemotherapy refractory disease is unknown. We designed a phase I/II study of X+TRAP to define the recommended phase II dose (RPTD), and assess the safety, tolerability, and clinical activity for the combination. Methods: Eligible pts with refractory, advanced solid tumors were enrolled in a 3+3 dose escalation cohort (ESC) to identify the RPTD. Cycle length was 21 days. Radiographic assessment occurred every 3 cycles. X was administered po bid on days 1-14. The dose of X was 850 mg/m2 bid in ESC cohort 1 and 1,000 mg/m2 bid in ESC cohort 2. TRAP was administered on day 1 of each cycle (6 mg/kg IV). Pts with mCRC that had progressed on all standard therapies were then enrolled in a single-arm, phase II expansion cohort (EXP) and treated at the RPTD. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Results: As of 6/19/2015, 55 pts were evaluable for toxicity (13 ESC; 42 EXP) and 47 pts were evaluable efficacy (12 ESC; 35 EXP). In the phase I ESC cohorts, 3 DLTs occurred (1/6 cohort 1; 2/6 cohort 2): GI perforation (1), oral mucositis (1), and fatigue (1). The RPTD was X (850 mg/m2 po bid, days 1-14) and TRAP (6 mg/kg IV, day 1). In the ESC and EXP cohorts, there were no treatment related grade 4/5 adverse events (AEs). The most frequently reported treatment related AEs (grades 2+3; grade 3) were palmar-plantar erythrodysesthesia (36%; 5%), hypertension (29%; 20%), and oral mucositis (18%; 4%). Median follow up in the phase II EXP cohort was 9.3 mos (95% C.I., 6.5–11.1). Median PFS was 4.1 mos (95% C.I., 2.3-4.8). Response assessment in 35 pts (n; %): partial response (PR) (2; 6%); stable disease (SD) (12; 34%); SD > 6 mos (2; 6%). Median OS was 9.3 mos (95% C.I., 6.2–n/a). Conclusions: The combination of X+TRAP demonstrated an acceptable safety profile, with encouraging clinical activity at the RPTD. Recruitment for the phase II EXP cohort is now complete. Clinical trial information: NCT01661972.
Strickler, JH; Rangwala, FA; Rushing, C; Niedzwiecki, D; Altomare, I; Uronis, HE; Hsu, SD; Zafar, Y; Morse, M; Chang, DZ; Wells, JL; Blackwell, KL; Marcom, PK; Webb, AR; Dropkin, E; Arrowood, C; Hurwitz, H
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