A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Metastatic Colorectal Cancer,Colon Cancer,N-ras Gene Mutation,Colorectal Cancer,K-ras Gene Mutation,Colorectal Neoplasms
PROVIDER: 2150287 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Desmoplastic small round cell tumor (DSRCT) is a rare and incurable malignancy characterized by the oncogenic EWSR1-WT1 transcription factor. This study exploited a novel DSRCT patient-derived xenograft (PDX), which reproduces histomorphological and molecular characteristics of the paired clinical tumor, to comparatively assess the activity of cytotoxic and targeted anticancer agents. Anti-tumor effect was moderate for single-agent doxorubicin, pazopanib and larotrectenib [maximum tumor volume inhibition (max TVI): 55-66%] while trabectedin had a higher effect (max TVI: 82%). Single-agent vinorelbine, irinotecan and eribulin achieved a nearly complete tumor growth inhibition (max TVI: 96-98%), although tumors started to re-growth after the end of treatment. Combination of irinotecan with either eribulin or trabectedin resulted in complete responses which were maintained until the end of the experiment for irinotecan plus trabectedin. Irinotecan-based combinations almost completely abrogated the expression of proteins involved in the G2/M checkpoint preventing cell entrance in mitosis and induced apoptotic and necroptotic cell death. This study emphasizes the importance of patient-derived pre-clinical models to explore new treatments in DSRCT and fosters clinical investigation in the activity of irinotecan plus trabectedin.
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Project description:Intervention name : Drug: PF-05212384 Drug: Irinotecan
Dosage And administration of the intervention : PF-05212384: 30 minute IV infusion of PF-05212384 110 mg on days 2, 9, 16 and 23 of each cycle Irinotecan: 90 minutes IV infusion of irinotecan 180mg/m2 on days 1 and 15 of each cycle
Control intervention name : Drug: Cetuximub Drug: irinotecan
Dosage And administration of the control intervention : Cetuximab: 120 minute IV infusion of cetuximab 400 mg/m2 on cycle 1 day 1; 60 minute IV infusion of cetuximab 250 mg/m2 on day 8, 15, and 22 of each cycle and on day of each cycle after cycle 1. Irinotecan: 90 minutes IV infusion of irinotecan 180mg/m2 on days 1 and 15 of each cycle
Primary outcome(s): PFS
Study Design: Open, 2 arm, randomized controlled trial
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