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Trial record 1 of 1 for:    NCT00216086
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Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer

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ClinicalTrials.gov Identifier: NCT00216086
Recruitment Status : Terminated (Funding withdrawn)
First Posted : September 22, 2005
Results First Posted : June 6, 2016
Last Update Posted : June 6, 2016
Sponsor:
Collaborators:
Pfizer
Roche Pharma AG
Walther Cancer Institute
Information provided by (Responsible Party):
Gabi Chiorean, MD, Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE September 9, 2005
First Posted Date  ICMJE September 22, 2005
Results First Submitted Date  ICMJE January 5, 2016
Results First Posted Date  ICMJE June 6, 2016
Last Update Posted Date June 6, 2016
Study Start Date  ICMJE May 2005
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2016)
Pathological Complete Response (pCR) Rate [ Time Frame: 36 months ]
· To determine the pathological response rate of preoperative chemotherapy with capecitabine and irinotecan followed by combined modality chemoradiation with capecitabine in patients with locally advanced rectal cancer. Pathological response was defined in the protocol as the proportion of complete (pCR) and non-complete pathological response (pNCR) among all evaluable patients.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
· To determine the pathological response rate of preoperative chemotherapy with capecitabine and irinotecan followed by combined modality chemoradiation with capecitabine in patients with locally advanced rectal cancer.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2016)
  • Local and Distant Disease Recurrence Rates [ Time Frame: 36 months ]
    To determine the rates of local and distant disease recurrence after treatment.
  • Rate of Clinical Response [ Time Frame: 36 months ]
    To determine the rate of clinical response following induction chemotherapy with capecitabine and irinotecan, and also the overall clinical response after the completion of chemoradiation with capecitabine.
  • Disease-Free Survival [ Time Frame: 36 months ]
    The three year rate of Disease-Free Survival
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2005)
· To determine the toxicity of preoperative capecitabine in combination with irinotecan and concurrent chemoradiation with capecitabine in patients with locally advanced rectal cancer.· To determine the rates of local and distant disease recurrence afte
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
Official Title  ICMJE A Phase II Trial of Preoperative Capecitabine Plus Irinotecan Followed by Combined Modality Capecitabine and Radiation for Locally Advanced Rectal Cancer: Hoosier Oncology Group GI03-53
Brief Summary

Preoperative induction chemotherapy has been successfully used in a variety of malignancies and provides several advantages over postoperative therapy. Combination of 5-FU/Leucovorin/CPT-11 has demonstrated significantly better response rate than 5-FU/Leucovorin alone. Replacing 5-FU with oral capecitabine in combination with CPT-11 has emerged as a potentially more effective, safe and convenient treatment option for metastatic colorectal cancer. Capecitabine is also well tolerated in concurrent treatment with radiation. Recent data has shown that preoperative radiation appears to be significantly more effective in increasing resectability rates.

This trial will investigate the activity of capecitabine and CPT-11 combination in the preoperative setting followed by chemoradiation with capecitabine in locally advanced rectal cancer to improve response and decrease local recurrence. We will also study whether TS, TP, DPD and carboxyesterase expressions correlate with the objective response rate with this chemotherapy and chemoradiation regimen.

Detailed Description

OUTLINE: This is a multi-center study.

Biopsy per EUS

  • Irinotecan 200 mg/m2 IV, day 1
  • Capecitabine 1000* mg/m2 PO BID day 1-14 Repeat every three weeks for two cycles* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 825 mg/m2 PO BID

Beginning at week 7 or following recovery from chemotherapy:

  • Pelvic XRT 45 Gy/1.8 Gy/fx/qd+5.4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8 Gy/fx/qd for T4
  • Capecitabine 825* mg/m2 PO BID, 5 days/week, throughout XRT* For calculated creatinine clearance of 30-50 mL/min or patients > 70years old, capecitabine starting dose is 650 mg/m2 PO BID
  • Surgery within 8weeks following chemoradiotherapy
  • Adjuvant Chemotherapy at investigator's discretion

ECOG performance status 0 or 1

Hematopoietic:·

  • ANC count >1,500 mm3·
  • Platelets > 100,000/mm3·
  • Hemoglobin > 9g/dL
  • Prothrombin time (PT)/INR or PTT < 1.25 times upper limit of normal;

Hepatic:·

  • Bilirubin <1.5 times upper limit of normal
  • Alanine Transaminase (ALT) or Aspartate Transaminase (AST) <2.5 times the upper limit of normal

Renal:·

  • Adequate renal function by calculated creatinine clearance > 30 mL/min (by Cockroft and Gault)

Cardiovascular:·

  • No congestive heart failure requiring therapy or NYHA class II or greater or active angina or known myocardial infarction within 12 months prior to study
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rectal Cancer
Intervention  ICMJE
  • Drug: Capecitabine

    Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles

    *For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid

    Other Name: Xeloda
  • Drug: Irinotecan
    Irinotecan 200 mg/m2 IV, day 1
    Other Name: Camptosar
  • Procedure: EUS
    biopsy per EUS
  • Drug: Neoadjuvant Chemotherapy
    • Irinotecan 200 mg/m2 IV, day 1
    • Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles
    Other Names:
    • Camptosar
    • Xeloda
  • Procedure: Preoperative Radiation
    Pelvic XRT 45 Gy/1.8 GY/fx/qd+5/4 Gy/1.8 Gy/fx/qd for T3+9 Gy/1.8/Gy/fx/qd for T4
  • Procedure: Surgery
    Surgery within 8 weeks following chemoradiotherapy
  • Procedure: Adjuvant Chemotherapy
    Adjuvant chemotherapy at investigator's discretion
Study Arms  ICMJE Experimental: Investigational Treatment
  • Irinotecan 200 mg/m2 IV, day 1
  • Capecitabine 1000* mg/m2 po bid day 1-14; repeat every three weeks for two cycles

    • For calculated creatinine clearance of 30-50 mL/min or patients > 70 years old, capecitabine starting dose is 825 mg/m2 po bid
  • EUS
  • Neoadjuvant Chemotherapy
  • Preoperative Radiation
  • Surgery
  • Adjuvant Chemotherapy (at discretion of treating physician)
Interventions:
  • Drug: Capecitabine
  • Drug: Irinotecan
  • Procedure: EUS
  • Drug: Neoadjuvant Chemotherapy
  • Procedure: Preoperative Radiation
  • Procedure: Surgery
  • Procedure: Adjuvant Chemotherapy
Publications * Chiorean EG, Sanghani S, Schiel MA, Yu M, Burns M, Tong Y, Hinkle DT, Coleman N, Robb B, LeBlanc J, Clark R, Bufill J, Curie C, Loehrer PJ, Cardenes H. Phase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53. Cancer Chemother Pharmacol. 2012 Jul;70(1):25-32. doi: 10.1007/s00280-012-1883-1. Epub 2012 May 18.

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: January 22, 2009)
22
Original Enrollment  ICMJE
 (submitted: September 14, 2005)
29
Actual Study Completion Date  ICMJE May 2008
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the rectum < 15 cm from the anal verge without evidence of distant metastasis·
  • Measurable disease. ·
  • Either mobile cancers (with clinical stage T3 or T4 by endorectal ultrasound) or fixed cancer (defined as clinical T4 for this study) on palpation. ·
  • Malignant disease may not extend to the anal canal (across the dentate line)

Exclusion Criteria:

  • No prior chemotherapy or radiation therapy to the pelvis.
  • Patients with clinical stage T 1-2, N0 rectal cancer who are candidates for primary resection are not eligible·
  • No synchronous colonic cancer unless the synchronous tumor is Tis or T1 and has been completely resected·
  • Patients must not be taking warfarin·
  • No prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-Fluorouracil or known DPD deficiency.·
  • No known existing uncontrolled coagulopathy·
  • Negative pregnancy test·
  • No current breastfeeding·
  • No serious concomitant systemic disorders incompatible with the study· No prior malignancies with the exception of curatively treated basal or squamous carcinoma of the skin, carcinoma in-situ of the cervix, or any other cancer for which the patient has been disease-free for < 5 years.·
  • Patients must not be treated with any of the following while on protocol therapy or within 28 days prior to beginning protocol therapy: sorivudine, brivudine, cimetidine, allopurinol.
  • Patients on dilantin must have regular monitoring of dilantin levels.
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 NCT00216086
Other Study ID Numbers  ICMJE HOG GI03-53
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gabi Chiorean, MD, Hoosier Cancer Research Network
Study Sponsor  ICMJE Gabi Chiorean, MD
Collaborators  ICMJE
  • Pfizer
  • Roche Pharma AG
  • Walther Cancer Institute
Investigators  ICMJE
Study Chair: Elena Gabriela Chiorean, M.D. Hoosier Oncology Group, LLC
PRS Account Hoosier Cancer Research Network
Verification Date April 2016

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