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Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy in Treating Patients With Metastatic or Unresectable Locally Advanced Small Bowel Cancer

This study is currently recruiting participants.
Verified November 2012 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00433550
First received: February 8, 2007
Last updated: November 9, 2012
Last verified: November 2012
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, 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.

PURPOSE: This phase II trial is studying how well giving irinotecan together with oxaliplatin and capecitabine works as first-line therapy in treating patients with metastatic or unresectable locally advanced small bowel cancer.


Condition Intervention Phase
Small Intestine Cancer
 Drug: capecitabine
Drug: irinotecan hydrochloride
Drug: oxaliplatin
 Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed tumor response (complete or partial response) after 12 courses of study therapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Incidence of celiac disease [ Designated as safety issue: No ]
  • Correlation of celiac disease with incidence of grade 3 or greater gastrointestinal toxicity [ Designated as safety issue: Yes ]
  • UGT1A7 and UGT1A9 polymorphism [ Designated as safety issue: No ]
  • Tumor location [ Designated as safety issue: No ]
  • Effect of different drug doses on response rates and toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 33
Study Start Date: May 2007
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
 Drug: capecitabine
given orally
Drug: irinotecan hydrochloride
given IV
Drug: oxaliplatin
given IV
Experimental: 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. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
 Drug: capecitabine
given orally
Drug: irinotecan hydrochloride
given IV
Drug: oxaliplatin
given IV
Experimental: Group 3 (7/7 UGT1A1 genotype)
Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
 Drug: capecitabine
given orally
Drug: irinotecan hydrochloride
given IV
Drug: oxaliplatin
given IV

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00433550

  Show 115 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
National Cancer Institute (NCI)
Investigators
Study Chair: Robert McWilliams, MD Mayo Clinic
Investigator: Benjamin T. Marchello, MD CCOP - Montana Cancer Consortium
Investigator: Matthew P. Goetz, MD Mayo Clinic
Investigator: Aminah Jatoi, MD Mayo Clinic
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00433550     History of Changes
Other Study ID Numbers: CDR0000528263, NCCTG-N0543
Study First Received: February 8, 2007
Last Updated: November 9, 2012
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
small intestine adenocarcinoma
recurrent small intestine cancer

Additional relevant MeSH terms:
Ileal Diseases
Adenocarcinoma
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Intestinal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
 Duodenal Diseases
Intestinal Diseases
Jejunal Diseases
Oxaliplatin
Irinotecan
Capecitabine
Camptothecin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013