- Assess the confirmed tumor response in patients with metastatic or unresectable locally advanced adenocarcinoma of the small bowel treated with irinotecan hydrochloride, oxaliplatin, and capecitabine when dosed according to UGT1A1 genotype.
- Assess the toxicity of this regimen in these patients.
- Assess, preliminarily, whether celiac disease may affect toxicity and outcome in patients treated with this regimen.
- Assess, preliminarily, whether tumor origin (duodenal, jejunal, or ileal) affects response or survival in these patients.
OUTLINE: This is a prospective, multicenter study. Patients are assigned to 1 of 3 treatment groups based on UGT1A1 genotype.
- Group 1 (6/6 UGT1A1 genotype): Patients receive irinotecan hydrochloride IV over 90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 2-15.
- Group 2 (6/7 UGT1A1 genotype): Patients receive irinotecan hydrochloride as in group 1. They also receive oxaliplatin and capecitabine as in group 1 but at lower doses.
- Group 3 (7/7 UGT1A1 genotype): Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.
In all groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Blood and serum samples are collected at baseline for UGT1A1 genotyping, celiac disease testing, and research studies, including translational and pharmacologic studies.
After the completion of study treatment, patients are followed every 6 weeks for 2 years and then periodically thereafter.
PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.
- Histologically* or cytologically* confirmed small bowel adenocarcinoma
- Metastatic or unresectable locally advanced disease NOTE: *Biopsy may be of primary tumor or from a metastatic site if there is a primary small bowel tumor or currently or previously present.
- Measurable disease
- For patients with lesions ≥ 1 cm but < 2 cm, spiral CT scan imaging must be used for tumor assessments
- Confirmed UGT1A1 TA indel genotype of 6/6, 6/7, or 7/7
- No periampullary carcinoma or appendiceal cancer
- No known CNS metastases or carcinomatous meningitis
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastasis is present)
- Bilirubin normal for patients with 6/6 genotype (< 2 times ULN for patients with 6/7 or 7/7 genotype)
- Hemoglobin ≥ 9.0 g/dL
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active or uncontrolled infection
- No other concurrent malignancy, except for nonmelanoma skin cancer
- No preexisting sensory neuropathy ≥ grade 2
- No evidence of serious intercurrent illness, including any of the following:
- Unstable angina
- Symptomatic congestive heart failure
- Serious uncontrolled cardiac arrhythmia
PRIOR CONCURRENT THERAPY:
- At least 2 weeks since prior radiotherapy
- At least 4 weeks since prior major surgery
- No prior chemotherapy for advanced small bowel cancer
- Prior adjuvant fluorouracil/leucovorin calcium allowed provided last dose was ≥ 3 months ago
- No prior adjuvant oxaliplatin or irinotecan hydrochloride
- No prior radiotherapy to > 25% of bone marrow
- No concurrent sorivudine, brivudine, lamivudine, or stavudine
- No concurrent sargramostim (GM-CSF) or pegfilgrastim
Last updated: 11/09/2012