A phase II trial of dasatinib in patients with unresectable locally advanced or stage IV mucosal, acral, and solar melanomas: An Eastern Cooperative Oncology Group study (E2607).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. TPS312-TPS312 ◽  
Author(s):  
K. Kalinsky ◽  
S. J. Lee ◽  
D. P. Lawrence ◽  
J. M. Kirkwood
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Oncology Group ◽  
Oncology Group Study

Predictive biomarkers in a phase II trial of weekly carboplatin (CBDCA), paclitaxel (P), and cetuximab (C) induction and chemoradiation (CRT) in patients (pts) with resectable stage III/IVa,b head and neck squamous cell carcinoma (HNSCC): Eastern Cooperative Oncology Group E2303.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6081-6081
Author(s):  
Amanda Psyrri ◽  
Ju-Whei Lee ◽  
Maria Vasilakopoulou ◽  
Eirini Pectasides ◽  
Barbara Burtness ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Multivariable Analysis ◽  
Stage Iii ◽  
Disease Stage ◽  
Oncology Group ◽  
Hpv Status

6081 Background: We studied the addition of C to a sequential regimen of weekly CBDCA and P followed by CBDCA-P-radiation in pts with locally advanced resectable HNSCC. Tissue-based biomarkers may aid in pt selection for such approaches. Methods: Sixty-three eligible pts withoperablestage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly C, P and CBDCA x 6 followed by CRT with concurrent weekly C, paclitaxel, carboplatin. A tissue microarray was constructed and b-catenin, E-cadherin, Epidermal Growth Factor Receptor Variant III (EGFRVIII), insulin-like growth factor-1 receptor (IGF1R), NF-kappa b, p53, PI3Kp85, PI3Kp110a, PTEN, ΝRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each marker, time-to-event distributions (OS, PFS, and EFS) were estimated by Kaplan-Meier estimates and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate hazard ratios and test for significance, with primary site (oropharynx vs. non-oropharynx), disease stage (III vs. IV), and other important markers adjusted in the model. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: Based on the continuous scale, pRb tended to association with EFS (p=0.05). On multivariable analysis, low pRb level was a significant predictor for improved EFS (p=0.048). Our pRb data analysis was based on 32 pts with marker data available. Conclusions: pRb level is a potential predictive biomarker for response to cetuximab. HPV E7 oncoprotein binds and degrades pRb; therefore, low pRb protein level might be a surrogate marker for HPV association.Large prospective studies will be required to determine the association between pRb, HPV status and response to cetuximab in HNSCC.

A phase II trial of dasatinib in patients with unresectable locally advanced or stage IV mucosal, acral, and solar melanomas: An Eastern Cooperative Oncology Group study (E2607).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8522-8522
Author(s):  
Kevin Kalinsky ◽  
Sandra J. Lee ◽  
Donald P. Lawrence ◽  
A. John Iafrate ◽  
Darrell R. Borger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Critical Role ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Stage Iv ◽  
Primary Objective ◽  
Stage I ◽  
Kit Mutation

8522 Background: Pre-clinical studies report a critical role of c-KIT mutations in mucosal, acral, and solar melanomas. Clinical trials of KIT-directed therapy with imatinib and sunitinib demonstrate activity in these subtypes. Unlike other TKIs, dasatinib inhibitory activity is seen in melanoma cell lines with the most common KIT mutation at exon 11L576P. E2607 tests the efficacy of dasatinib in treatment-naïve or previously treated patients (pts) with these unresectable subtypes. Methods: Pts receive dasatinib 70 mg PO twice daily for this two-stage phase II trial. The primary objective is response rate (RR: RECIST). Stage I was open to KIT mutated (KIT+) and wild-type (KIT-) tumors with these subtypes (n=56). Depending upon the interim analysis, stage II would pre-select for KIT+. If the overall response rate were < 5%, the study would be terminated. Secondary objectives include progression-free survival (PFS), overall survival (OS), safety, and KIT mutation status. Results: Between May 2009-Dec 2010, 57 pts have been accrued to stage I. Of 54 (2 no therapy, 1 ineligible), 26 have mucosal (48%), 13 acral (24%), and 15 solar melanomas (28%). As of Jan 2012, the median f/u is 15 months (mo, range: 4-24 mo). Best responses (n=52) are 1 complete (CR: 2%), 3 partial (PR: 6%), 13 stable disease (25%), 29 progression (56%), and 6 unevaluable (11%). 51/52 have progressed (median PFS: 1.9 mo, 95% CI: 1.5-2.8) and 40/54 died (median OS: 7.4 mo, 5.7-10.8). KIT status has been assessed in 42 pts: 39 KIT- (93%) and 3 KIT+ (7%). PR is seen in 1/39 KIT-. All KIT- have died: median PFS (1.8 mo, 95% CI: 1.4-2.9) and OS (6.8 mo, 95% CI: 5.2-10.8). Of the 3 KIT+ (1 acral, 2 mucosal), 2 have died (PFS 1.4-2.5 mo, OS: 1.4-10.5 mo), and 1 refused f/u (OS: 13.3+ mo). The pt with a CR is alive at 14.4+ mo (unknown KIT status). Toxicities include 1 grade IV (elevated lipase) and grade III dyspnea (n=7), nausea (n=6), and vomiting (n=3). Conclusions: Further evaluation of dasatinib should be pursued in pts selected for KIT+ and subtype, given the lack of promising results in Kit-(<5% RR). The current trial is revised to enroll only KIT+ acral, mucosal, and vulvovaginal melanomas and available via CTSU.

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