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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00433550
First received: February 8, 2007
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Confirmed tumor response [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to disease progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: May 2007
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 capecitabine PO BID on days 2-15
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.
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.
Drug: capecitabine
given orally
Drug: irinotecan hydrochloride
given IV
Drug: oxaliplatin
given IV

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess the confirmed tumor response of the combination of oxaliplatin, irinotecan (irinotecan hydrochloride), and capecitabine in patients with advanced adenocarcinoma of the small bowel when dosed according to UGT1A1 genotype.

SECONDARY OBJECTIVES:

I. To assess the toxicity of this regimen in these groups of patients. II. To gain preliminary data on whether microsatellite instability influences outcome within this arm.

III. To gain preliminary data on whether evidence of celiac disease may affect toxicity and outcome.

IV. To gain preliminary data on whether site of tumor origin (duodenal, jejunal, or ileal) affects response or survival.

OUTLINE: Patients are assigned to 1 of 3 treatment groups based on UGT1A1 genotype.

GROUP 1 (6/6 UGT1A1 genotype): Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and oxaliplatin IV over 2 hours on day 1 and capecitabine orally (PO) twice daily (BID) 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.

After the completion of study treatment, patients are followed every 6 weeks for 2 years and then periodically thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433550

  Show 115 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Robert McWilliams, MD Mayo Clinic
  More Information

Additional Information:
No publications provided by Alliance for Clinical Trials in Oncology

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00433550     History of Changes
Other Study ID Numbers: NCCTG-N0543, NCI-2009-00650, CDR0000528263
Study First Received: February 8, 2007
Last Updated: July 23, 2015
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Camptothecin
Capecitabine
Irinotecan
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 03, 2015