Phase II study of biweekly cetuximab+irinotecan therapy for unresectable colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Unresectable Colorectal Cancer
PROVIDER: 2626733 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: biweekly administration of cetuximab
Primary outcome(s): Response rate
Study Design: Single arm Non-randomized
| 2626732 | ecrin-mdr-crc
Project description:Interventions: Biweekly cetuximab plus irinotecan
Primary outcome(s): response rate
Study Design: Single arm Non-randomized
| 2617437 | ecrin-mdr-crc
Project description:Interventions: Cetuximab 500 mg/m2/biweekly CPT-11 150 mg/m2/biweekly
Primary outcome(s): response rate
Study Design: Single arm Non-randomized
| 2618942 | ecrin-mdr-crc
Project description:Efficacy and safety of biweekly cetuximab plus irinotecan were evaluated to provide guidance for its use in Japan as third-line treatment for pretreated metastatic colorectal cancer (mCRC) patients harboring wild-type KRAS exon 2. Objective response rate (ORR) was used as primary endpoint based on an expected proportion of 0.23 with confidence width of 0.298 (95% CI, 0.105-0.403), which showed 35 to be the minimal participant number. Forty patients, refractory to first- and second-line chemotherapy containing irinotecan, oxaliplatin, and fluoropyrimidine, were enrolled. ORR and disease control rate were 25.0% (95% CI: 11.5-38.4) and 72.5% (95% CI: 56.8-86.4), respectively. Median progression-free survival (PFS), overall survival (OS), and number of courses were 5.70 months (95% CI: 2.7-7.9), 15.1 months (95% CI: 11.8-19.0), and 10.5 (range: 3.0-31.0), respectively. Grade 3 adverse events were skin toxicity (12.5%), diarrhea (10.0%), neutropenia (5.0%), febrile neutropenia (5.0%), nausea (5.0%), anorexia (5.0%), and fatigue (2.5%). Cmax mean was 723.2 μg/mL after first dose. High area under the curve (AUC)last variance was associated with t1/2 range of 131.2-1209.6 hours (median, 174.4 hours). Early tumor shrinkage (ETS) and median depth of response were 25.0% and 13.0%, respectively. Mutation frequencies in KRAS exon 3 or 4, NRAS, BRAF, and PIK3CA were 5.5%, 2.7%, 8.3%, and 5.5%, respectively. Multivariate Cox regression analysis assessed whether any gene mutations and ETS are predictors for PFS, and whether performance status, synchronous metastasis, and ETS are predictors for OS. Importantly, the data provide guidance for a biweekly cetuximab plus irinotecan regimen in mCRC patients.
| S-EPMC6113428 | biostudies-literature
Project description:Interventions: Irinotecan with biweekly cetuximab combination chemotherapy Cetuximab biweekly administration 500mg/m2(day1,15,29, , , ) Irinotecan biweekly administration 150mg/m2(day1,15,29, , ,)
Primary outcome(s): Response rate
Study Design: Single arm Non-randomized
| 2618233 | ecrin-mdr-crc
Project description:Interventions: administration of cetuximab biweekly
Primary outcome(s): Response rate
Study Design: Single arm Non-randomized
| 2626734 | ecrin-mdr-crc
Project description:Abstract Background. Epidermal growth factor receptor (EGFR) is a targetable molecule in basal-like breast cancer, which comprises most “triple negative” breast cancer (TNBC), the only breast cancer subtype without established targeted therapy. Methods. In this randomized phase II trial, metastatic TNBC patients received the anti-EGFR antibody cetuximab (250mg/kg/week iv) with carboplatin (AUC2/wk iv) added on progression, or concomitant cetuximab + carboplatin. Molecular subtyping was done on archival specimens and those with accessible tumors provided fresh tissue, before and after 7-14 days of therapy, for microarray analyses to explore EGFR pathway inhibition. Results. Of 102 TNBC patients 74% were of the basal-like molecular subtype. Response rate to cetuximab was 6% (2/31), and was 16% (4/25) to cetuximab + carboplatin after progression. Upfront cetuximab + carboplatin produced responses in 17% (12/71); 31% responded or had prolonged disease stabilization. Time to progression was 2.1 months (95% CI 1.8-5.5) and overall survival 10.4 months (95% CI 7.7-13.1) for those treated with the combination regimen. Among 16 patients with evaluable serial biopsies, genomic patterns of the EGFR pathway showed activated status in 13 and inhibition by therapy in 5. Conclusions. While most TNBC were basal-like, a significant proportion were different subtypes. The aggressive nature of metastatic TNBC leads to limited survival. Despite a promising preclinical rationale and evidence of EGFR pathway activation in most, targeted treatment with cetuximab as a single agent had marginal activity and cetuximab added to carboplatin demonstrated modest activity. Serial biopsies as part of metastatic breast cancer studies are feasible, and this study confirmed that the EGFR pathway was inhibited by therapy in only a minority suggesting ligand-independent activation in most tumors. Tissue acquisition and drug selection based upon individualized pathway activation status should be an important part of future studies of TNBC. This series contains 36 microarrays that are from 18 patients with fresh frozen tissue available from the metastatic site. Pretreatment samples (Bx0) are available for two patients. Pretreatment and post single agent treatment (7-14 days after start of treatment with cetuximab; BxSingle) are available for three patients. Pretreatment and post combination treatment (7-14 days after start of treatment with cetuximab plus carboplatin; BxCombo) are available for eight patients. Two patients have a pretreatment sample, a sample after 7-14 days of treatment with single agent cetuximab, and a third sample 7-14 days on cetuximab plus carboplatin after switching to the combination arm upon progression on the single agent arm. Samples were hybridized with Stratagene common reference spiked with RNA from two breast cancer cell lines (ME16C and MCF-7) on Custom 1x44K Agilent microarrays. Arrays were scanned on an Axon 4000B scanner and analyzed with GenePix Pro software.
2012-07-13 | E-GEOD-23428 | biostudies-arrayexpress
Project description:Abstract Background. Epidermal growth factor receptor (EGFR) is a targetable molecule in basal-like breast cancer, which comprises most “triple negative” breast cancer (TNBC), the only breast cancer subtype without established targeted therapy. Methods. In this randomized phase II trial, metastatic TNBC patients received the anti-EGFR antibody cetuximab (250mg/kg/week iv) with carboplatin (AUC2/wk iv) added on progression, or concomitant cetuximab + carboplatin. Molecular subtyping was done on archival specimens and those with accessible tumors provided fresh tissue, before and after 7-14 days of therapy, for microarray analyses to explore EGFR pathway inhibition. Results. Of 102 TNBC patients 74% were of the basal-like molecular subtype. Response rate to cetuximab was 6% (2/31), and was 16% (4/25) to cetuximab + carboplatin after progression. Upfront cetuximab + carboplatin produced responses in 17% (12/71); 31% responded or had prolonged disease stabilization. Time to progression was 2.1 months (95% CI 1.8-5.5) and overall survival 10.4 months (95% CI 7.7-13.1) for those treated with the combination regimen. Among 16 patients with evaluable serial biopsies, genomic patterns of the EGFR pathway showed activated status in 13 and inhibition by therapy in 5. Conclusions. While most TNBC were basal-like, a significant proportion were different subtypes. The aggressive nature of metastatic TNBC leads to limited survival. Despite a promising preclinical rationale and evidence of EGFR pathway activation in most, targeted treatment with cetuximab as a single agent had marginal activity and cetuximab added to carboplatin demonstrated modest activity. Serial biopsies as part of metastatic breast cancer studies are feasible, and this study confirmed that the EGFR pathway was inhibited by therapy in only a minority suggesting ligand-independent activation in most tumors. Tissue acquisition and drug selection based upon individualized pathway activation status should be an important part of future studies of TNBC.
2012-07-14 | GSE23428 | GEO
Project description:Interventions: Irinotecan plus S-1 (IRSI) with biweekly cetuximab combination therapy 1)Irinotecan 100 mg/m2 day1,15, 30 biweekly until PD 2)S-1 80mg [BSA<1.25m2] or 100mg [1.25m2<BSA<1.5m2] or 120mg [1.5m2<BSA]/body/day, day 1-14, q4weeks 3)Cetuximab 500mg/m2 day 1, 15, 29 biweekly until PD
Primary outcome(s): Response rate
Study Design: Single arm Non-randomized
| 2622245 | ecrin-mdr-crc
Project description:Lessons learnedTrials focusing on unresectable multifocal glioblastoma are needed because of the extremely poor prognosis and challenges in receiving standard therapy, such as concurrent radiation and chemotherapy.Developing a strategy to chemically debulk tumors before radiation and/or surgery is warranted.BackgroundExtent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection. We conducted a phase II trial of upfront therapy with bevacizumab (BV), irinotecan (CPT-11), and temozolomide (TMZ) prior to chemoradiation in patients with unresectable, subtotally resected, and/or multifocal GBM.MethodsPatients received up to 4 cycles of TMZ at 200 mg/m(2) per day on days 1-5 (standard dosing) and BV at 10 mg/kg every 2 weeks on a 28-day cycle. CPT-11 was given every 2 weeks on a 28-day cycle at 125 mg/m(2) or 340 mg/m(2) depending on antiepileptic drugs. Magnetic resonance imaging of the brain was done every 4 weeks, and treatment continued as long as there was no tumor progression or unmanageable toxicity. The primary endpoint was tumor response rate, with a goal of 26% or greater.ResultsForty-one patients were enrolled from December 2009 to November 2010. Radiographic responses were as follows: 9 patients (22.0%) had partial response, 25 (61.0%) had stable disease, and 2 (4.9%) had progression; 5 patients were not assessed. Cumulative response rate was 22%. Median overall survival was 12 months (95% confidence interval: 7.2-13.5 months).ConclusionUpfront treatment with BV, TMZ, and CPT-11 is tolerable and can lead to radiographic response in unresectable and/or subtotally resected GBM.
| S-EPMC4492239 | biostudies-literature