NCCTG Status Report for Study N May 2010

Transcription

1 Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for dvanced Small Bowel denocarcinoma Purpose of - Primary Goal Study: 1) To assess the efficacy of the combination of oxaliplatin, irinotecan, and capecitabine in patients with advanced adenocarcinoma of the small bowel, when dosed according to UGT11 genotype. - Secondary Goals 1) To assess the toxicity of this regimen in these groups of patients. 2) To gain preliminary data on whether microsatellite instability influences outcome within this arm. 3) To gain preliminary data on whether evidence of celiac disease may affect toxicity and outcome. 4) To gain preliminary data on whether site of tumor origin (duodenal, jejunal, or ileal) affects response or survival. Study Chairs: obert. cwilliams.d. Benjamin T. archello.d. QC Specialist: Carol. Leonard Statistician: ichelle. ahoney.s. Nurse esource: Nancy L. Vaught.N., O.C.N. Status: 05/11/2007 ctivated Projected Number of Patients: 36 Excluded: 1 Final ccrual: N Stratification None Schema: egistration rm (6/6 UGT11 genotype) rm B (6/7 UGT11 genotype) rm C (7/7 UGT11 genotype) Treating Schedule: rm gent Dose oute Days Freq Irinotecan 150 mg/m2 IV over 90 minutes in weeks ml NS or D5W Oxaliplatin 100 mg/m2 IV over 2 hours in 250 ml 1 3 weeks D5W after CPT-11 Capecitabine 1600 mg/m2/day PO, divided twice daily weeks (800 mg/m2 two times daily) B Irinotecan 150 mg/m2 IV over 90 minutes in 500 ml NS or D5W 1 3 weeks NCCTG Committee N Page 1 of 7

2 rm gent Dose oute Days Freq B Oxaliplatin 85 mg/m2 IV over 2 hours in 250 ml 1 3 weeks D5W after CPT-11 B Capecitabine* 400 mg/m2/day PO, divided twice daily weeks (200 mg/m2 two times a day) C Irinotecan 75 mg/m2 IV over 90 minutes in weeks ml NS or D5W C Oxaliplatin 85 mg/m2 IV over 2 hours in 250 ml 1 3 weeks D5W after CPT-11 C Capecitabine* 400 mg/m2/day PO, divided twice daily (200 mg/m2 two times a day) weeks *Patients on rms B and C may have dose of capecitabine increased up to 800 mg/m2 beginning on cycle 2 if no Grade 3 toxicities are encountered on cycle 1, at discretion of treating physician. Study Design: This is a two-stage, three-outcome design (Fleming, Goldberg-Sargent) evaluating the confirmed tumor response within the first 12 cycles of treatment. Stage 1 will accrue 16 evaluable patients. If we see 1 or 0 successes in stage 1 we will conclude that the regimen is not effective. Otherwise we will continue to accrue an additional 17 patients. If 5 or fewer successes are observed in the first 33 evaluable patients then we will consider this regimen ineffective. If there are 7 or more successes we may recommend further testing. If there are exactly 6 successes we will use other criteria (e.g., patient tolerance) to determine if further study is warranted. ccrual: s of the freeze date of arch 23, 2010, 20 patients (9 arm, 9 arm B, and 2 arm C) have been accrued to this study. Please see the accrual table. Patient Characteristics: The distribution of patient characteristics at study entry is located in the Baseline Characteristics Table. dverse s: s of the freeze date of arch 23, 2010, 19 patients (9 arm, 8 arm B, 2 arm C) are evaluable for toxicity. Five patients have experienced a grade 4 adverse event: Two patients experienced neutropenia, one patient experienced fatigue, one patient experienced small intestinal obstruction, and one patient experienced both leukopenia and neutrophil count decreased. No grade 5 adverse events have been reported. Please see the dverse Table for more details. Study Status: Study is open. NCCTG Committee N Page 2 of 7

3 ccrual Table: andomizing embership Total Entered Past 6 onths Past 12 onths nn rbor Duluth Grand Forks N CGOP ayo etro N ontana apid City Sioux City Toledo Total embership ccrual Baseline Characteristics Table: Gender Characteristics rm rm B f m Genotype 6/ / / Primary Tumor Site Duodenum Jejunum Ileum ace White rm C Grade 4/5 and ost Frequent dverse Table: rm Evaluable Patients: 9 rm B Evaluable Patients: 8 rm C Evaluable Patients: 2 dverse aximum Severity Per Patient Hematology LYPHOPENI NCCTG Committee N Page 3 of 7

4 dverse aximum Severity Per Patient THOBOCYTOPENI B NEI B LEUKOPENI B NEUTOPHIL COUNT DECESED B C llergy/immunology HYPESENSITIVITY Cardiovascular EDE Constitutional Symptoms FTIGUE B WEIGHT LOSS Dermatology/Skin LOPECI B SKIN XN-HND/FOOT Gastrointestinal NOEXI NUSE B C DEHYDTION NCCTG Committee N Page 4 of 7

5 dverse aximum Severity Per Patient C DYSPEPSI DIHE B GSTITIS UCOSITIS OL B OBSTUCTION GSTIC C SLL INTESTINL OBSTUCTION TSTE VOITING B C OL CV S CE Hepatic SGOT (ST) SGPT (LT) LKLINE PHOSPHTSE INCESED NCCTG Committee N Page 5 of 7

6 dverse aximum Severity Per Patient BILIUBIN Infection/Febrile Neutropenia FEBILE NEUTOPENI PNEUONI G 3-4 NC NVITIS CLOSTIDIL INFECTN PNEUONI G 0-2 NC NV INFECTN etabolic/laboratory HYPEGLYCEI C HYPEKLEI HYPOKLEI Neurology INSONI DIZZINESS NEUO-SENSOY B NCCTG Committee N Page 6 of 7

7 dverse aximum Severity Per Patient NEUO Pain BDOINL PIN Pulmonary COUGH B DYSPNE enal /Genitourinary UETEL OBSTUCTION ENL FILUE aximum Grade dverse B C NCCTG Committee N Page 7 of 7