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

Sponsors and Collaborators:	North Central Cancer Treatment Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00433550

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 II

MedlinePlus related topics: Cancer Intestinal Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride Capecitabine Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

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:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1 (6/6 UGT1A1 genotype): Experimental 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
Group 2 (6/7 UGT1A1 genotype): Experimental 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
Group 3 (7/7 UGT1A1 genotype): Experimental 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 confirmed small bowel adenocarcinoma
- Metastatic or unresectable locally advanced disease
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 169 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

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

Study ID Numbers:	CDR0000528263, NCCTG-N0543
Study First Received:	February 8, 2007
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00433550
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

small intestine adenocarcinoma
recurrent small intestine cancer

Study placed in the following topic categories:

Jejunal Neoplasms
Capecitabine
Digestive System Neoplasms
Gastrointestinal Diseases
Irinotecan
Intestinal Diseases
Ileal Diseases
Camptothecin
Recurrence

Intestinal Neoplasms
Duodenal Neoplasms
Oxaliplatin
Digestive System Diseases
Ileal Neoplasms
Gastrointestinal Neoplasms
Adenocarcinoma
Duodenal Diseases

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Jejunal Diseases
Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009