E7208: A randomized phase II trial of irinotecan and cetuximab (IC) versus IC plus ramucirumab (ICR) in second-line therapy of KRAS wild-type colorectal cancer (CRC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS3665-TPS3665 ◽  
Author(s):  
Howard S. Hochster ◽  
Paul J. Catalano ◽  
Edith P. Mitchell ◽  
Deirdre Jill Cohen ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Wild Type ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii

E7208: A randomized phase II trial of irinotecan and cetuximab (IC) versus IC plus ramucirumab (ICR) in second line therapy of KRAS wild type colorectal cancer (CRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS793-TPS793 ◽  
Author(s):  
Howard S. Hochster ◽  
Paul J. Catalano ◽  
Edith P. Mitchell ◽  
Deirdre Jill Cohen ◽  
Peter J. O'Dwyer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Bowel Perforation ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii ◽  
Grade 3

TPS793 Background: Anti-angiogenic therapy for CRC has been accepted as standard therapy with approval of bevacizumab (bev) in both first-line and second-line settings. At the time this study was started, the benefit of continuing an anti-angiogenic in second line therapy was unproven. Ramucirumab (RAM, IMC 1121b) is a humanized antibody directed against the VEGF-R2 receptor, which may prove to have different activity compared to anti-VEGF antibody (bev). Additionally, while combining the anti-EGFR antibody, cetuximab (CMAB), with bev in first-line unselected patients was not effective, it is unknown whether the same may be true with RAM plus CMAB in a second-line setting for KRAS-selected patients. Methods: The study was designed as a randomized phase II trial with 147 patients assigned to IC = irinotecan (I) 180 mg/m2 IV plus CMAB 500 mg/m2 IV q2w versus ICR = IC plus RAM 8 mg/kg IV q2w. Eligibility included prior treatment on one prior oxaliplatin and bev-containing regimen and progression within 42 days of last bev, PS 0-1, KRAS codon 12,13 wild-type and standard other chemo and bev criteria. Doses were modified for neutropenia, diarrhea, mucositis, rash and grade 3 other toxicities. The study was activated 10/8/10. The first 35 patients were enrolled and accrual was held 6/24/12 for toxicity analysis per protocol. More grade 3 events of mucositis, diarrhea, neutropenia and perforation events (including peri-rectal abscesses) were seen in the ICR arm. The study has been modified reflect the actual doses received, and now uses modified ICR (mICR) = I 150 mg/m2, CMAB 400 mg/m2 and RAM 6 mg/kg IV q2w. The study was re-activataed in May 2014. An additional 100 pts will be accrued to the revised study, giving 85% power to detect improved median PFS from 4.5 to 7.65 months. New eligibility criteria include any progression from first-line chemo (on or off), normal albumin, no bowel perforation or obstruction in last 6 months. This study is now open to accrual in ECOG-ACRIN and in SWOG with endorsement, and via CTSU. Clinical trial information: NCT01079780.

Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3591-3591 ◽  
Author(s):  
M. R. Moore ◽  
C. Jones ◽  
G. Harker ◽  
F. Lee ◽  
B. Ardalan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Neuropathy ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Grade 3

3591 Background: DJ-927, a novel oral tubulin depolymerization inhibitor, causes apoptosis and DNA cell division arrest. It is not a substrate for the MDR and has excellent activity in preclinical colorectal cancer models. Methods: We are conducting a two-stage, multi-center, phase II trial to assess the efficacy of DJ-927 administered initially as second-line therapy following failure of irinotecan or oxaliplatin based therapy (n= 39). DJ-927 is given as a single oral dose on day 1 of a 21-day cycle at a dose range of 27 - 35 mg/m2. Results: Thirty-nine patients were enrolled, including 14 with prior irinotecan based therapy and 25 who had received prior oxaliplatin therapy. The median age was 56 years (range: 30–87) and the median ECOG PS at baseline was 1 (range: 0–2). A total of 155 courses (range: 1–24) have been administered with a median of 2 courses. Nine patients required dose reduction due to toxicity. Thirty-seven patients were evaluable for efficacy. There were 2 CRs and 2 PRs (10.3%) reported that were confirmed as per RECIST criteria. Fourteen patients (35.9%) had SD, including 6 patients (15.4%) with SD >12 weeks. The most common Grade 3 or 4 AEs were neutropenia (48.7%), fatigue (10.3%), neuropathy (7.8%), and nausea (5.0%).Six patients experienced febrile neutropenia, all requiring hospitalization but tolerated treatment with subsequent dose reduction. There were 13 episodes (33.3%) of peripheral neuropathy reported; however, only 3 (7.8%) were grade 3 or 4. Six patients withdrew due to adverse events. Conclusions: The results of this study indicate activity of DJ-927 as second line therapy in patients with metastatic colorectal cancer. Severe toxicity was generally limited to reversible neutropenia and peripheral neuropathy. This novel oral agent is well tolerated and warrants further evaluation in combination with other active agents. [Table: see text]

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