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Trial record 1 of 1 for:    NCT00433550
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Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy in Treating Patients With Metastatic or Unresectable Locally Advanced Small Bowel Cancer

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ClinicalTrials.gov Identifier: NCT00433550
Recruitment Status : Completed
First Posted : February 12, 2007
Results First Posted : August 24, 2017
Last Update Posted : August 24, 2017
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Pfizer
Sanofi
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE February 8, 2007
First Posted Date  ICMJE February 12, 2007
Results First Submitted Date  ICMJE February 15, 2017
Results First Posted Date  ICMJE August 24, 2017
Last Update Posted Date August 24, 2017
Study Start Date  ICMJE May 2007
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
Confirmed Tumor Response Rate (Proportion of Participants With Complete Response) [ Time Frame: 36 weeks ]
Evaluated using RECIST version 1.0. Confirmed tumor response rate was defined as achieving partial response (PR) or complete response (CR) in two consecutive assessments at least 6 weeks apart. CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. The confirmed response rate is reported as the number of participants with confirmed responses divided by the number of evaluated participants.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2007)
Confirmed tumor response (complete or partial response) after 12 courses of study therapy
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
  • Overall Survival [ Time Frame: Up to 2 years ]
    Overall survival will be defined as the time from registration to death. Patients lost to follow-up for this endpoint will be censored at the date of last contact (i.e., last known alive). The distribution of overall survival will be estimated using Kaplan-Meier methodology.
  • Progression Free Survival [ Time Frame: Up to 2 years ]
    Time to disease progression is defined as the time from registration to the earlier of documentation of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The distribution of time to progression will be estimated using Kaplan-Meier methodology.
  • Duration of Response [ Time Frame: Up to 2 years ]
    Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Duration of response will be analyzed using Kaplan-Meier methods.
  • Time to Treatment Failure [ Time Frame: Up to 2 years ]
    Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal. If the patient is considered to have had a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they are removed from treatment. Time to treatment failure will be analyzed using Kaplan-Meier methods.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2007)
  • Overall Survival
  • Time to disease progression
  • Duration of response
  • Time to treatment failure
  • Incidence of celiac disease
  • Correlate celiac disease with incidence of grade 3 or greater gastrointestinal toxicity
  • UGT1A7 and UGT1A9 polymorphism
  • Tumor location
  • Dose differences effect on response rates and toxicity
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy in Treating Patients With Metastatic or Unresectable Locally Advanced Small Bowel Cancer
Official Title  ICMJE A Phase II Trial of Pharmacogenetic-Based Dosing of Irinotecan, Oxaliplatin, and Capecitabine as First-Line Therapy for Advanced Small Bowel Adenocarcinoma
Brief 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.
Detailed Description

PRIMARY OBJECTIVE:

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:

  1. To assess the toxicity of this regimen in these groups of patients.
  2. To gain preliminary data on whether microsatellite instability influences outcome within this arm.
  3. To gain preliminary data on whether evidence of celiac disease may affect toxicity and outcome.
  4. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Small Intestine Adenocarcinoma
  • Recurrent Small Intestine Cancer
Intervention  ICMJE
  • Drug: capecitabine
    given orally
  • Drug: irinotecan hydrochloride
    given IV
  • Drug: oxaliplatin
    given IV
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: capecitabine
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
  • 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.
    Interventions:
    • Drug: capecitabine
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
  • Experimental: Group 3 (7/7 UGT1A1 genotype)
    Patients receive irinotecan hydrochloride, oxaliplatin, and capecitabine as in group 1 but at lower doses.
    Interventions:
    • Drug: capecitabine
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
Publications * Goetz MP, McKean HA, Reid JM, Mandrekar SJ, Tan AD, Kuffel MA, Safgren SL, McGovern RM, Goldberg RM, Grothey AA, McWilliams R, Erlichman C, Ames MM. UGT1A1 genotype-guided phase I study of irinotecan, oxaliplatin, and capecitabine. Invest New Drugs. 2013 Dec;31(6):1559-67. doi: 10.1007/s10637-013-0034-9. Epub 2013 Oct 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2007)
33
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00433550
Other Study ID Numbers  ICMJE NCCTG-N0543
NCI-2009-00650 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000528263 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Pfizer
  • Sanofi
Investigators  ICMJE
Study Chair: Robert McWilliams, MD Mayo Clinic
PRS Account Alliance for Clinical Trials in Oncology
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP