Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy in Treating Patients With Metastatic or Unresectable Locally Advanced Small Bowel Cancer
Condition: Small Intestine Adenocarcinoma; Recurrent Small Intestine Cancer
MeSH terms: Adenocarcinoma; Intestinal Neoplasms
Intervention: capecitabine; irinotecan hydrochloride; oxaliplatin
Intervention description: given orally; given IV; given IV
Intervention MeSH terms: Capecitabine; Oxaliplatin; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving irinotecan hydrochloride together with
      oxaliplatin and capecitabine works as first-line therapy in treating patients with metastatic
      or unresectable locally advanced small bowel cancer. Drugs used in chemotherapy, such as
      irinotecan hydrochloride, oxaliplatin, and capecitabine, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      more than one drug (combination chemotherapy) may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria

          -  Confirmation UDP glucuronosyltransferase 1 family, polypeptide A complex locus
             (UGT1A1) TA indel genotype of 6/6, 6/7, or 7/7 after pre-registration but prior to
             registration

          -  Patient willingness to provide a serum sample for analysis for celiac disease (tissue
             transglutaminase antibodies)

          -  Small bowel adenocarcinoma, either metastatic or locally advanced and not surgically
             resectable; NOTE: periampullary carcinoma and appendiceal cancer are not eligible

          -  Histologic or cytologic confirmation of adenocarcinoma consistent with small bowel
             origin; biopsy can be of primary tumor or can be from a metastatic site if there is a
             primary small bowel tumor currently or previously present

          -  Measurable disease; for patients with lesions >= 1 cm but < 2 cm, spiral computed
             tomography (CT) scan imaging must be used for tumor assessments

          -  Life expectancy >= 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  >= 4 weeks since prior major surgery to time of registration

          -  >= 2 weeks from completion of any radiation treatment

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Serum glutamic oxaloacetic transaminase (SGOT) =< 5 x upper normal limit (UNL); =< 2.5
             x UNL if no liver metastases

          -  Total bilirubin:

               -  For 6/6 patients: =< upper limit of normal (ULN)

               -  For 6/7 or 7/7 patients: =< 2.0 x ULN

          -  Hemoglobin >= 9.0 g/dL

          -  Creatinine =< 1.5 x UNL (if > 1.5 x UNL, calculated creatinine clearance should be
             checked.; if it is > 60 mL/min, then the patient is eligible for the study)

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

        Exclusion Criteria

          -  Prior chemotherapy regimen for advanced small bowel cancer (prior adjuvant
             chemotherapy with fluorouracil (5FU)/leucovorin is permitted if last dose was
             administered >= 3 months prior to registration); prior oxaliplatin or irinotecan use
             as adjuvant therapy is not permitted

          -  Prior radiotherapy to > 25% of bone marrow

          -  Active or uncontrolled infection

          -  Evidence of serious intercurrent illness (e.g., unstable angina, symptomatic
             congestive heart failure, serious uncontrolled cardiac arrhythmia)

          -  Pregnant women; women of child-bearing potential and men must agree to use adequate
             contraception (diaphragm, birth control pills, injections, foams, intrauterine device
             [IUD], or abstinence, etc.) for the duration of study participation; if a woman
             becomes pregnant or suspects that she is pregnant while participating in this study,
             she should inform her treating physician immediately and all study treatment
             discontinued

          -  Nursing women; breast-feeding should be discontinued when the mother is treated with
             these agents

          -  Men or women of childbearing potential who are unwilling to employ adequate
             contraception

          -  Current evidence of other malignancy besides small bowel adenocarcinoma, with
             exception of non-melanoma skin cancer

          -  Known central nervous system metastases or carcinomatous meningitis

          -  Preexisting sensory neuropathy >= grade 2 from any cause interfering with function

          -  Concurrent therapy with sorivudine, brivudine, lamivudine, or stavudine