Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer

This study has been terminated.
(Slow accrual.)
Sponsor:
Collaborators:
Pfizer
Roche Pharma AG
Walther Cancer Institute
Information provided by:
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00216086
First received: September 9, 2005
Last updated: April 28, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Drug: Capecitabine
Drug: Irinotecan
Procedure: EUS
Drug: Neoadjuvant Chemotherapy
Procedure: Preoperative Radiation
Procedure: Surgery
Procedure: Adjuvant Chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • · 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. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • · 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 [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: January 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: I

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

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

Drug: Irinotecan
Irinotecan 200 mg/m2 IV, day 1
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
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

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
  Eligibility

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

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.
  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: NCT00216086

Locations
United States, Indiana
Elkhart Clinic
Elkhart, Indiana, United States, 46515
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Center for Cancer Care at Goshen Health System
Goshen, Indiana, United States, 46527
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Quality Cancer Center (MCGOP)
Indianapolis, Indiana, United States, 46202
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Center for Cancer Care, Inc., P.C.
New Albany, Indiana, United States, 47150
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
AP&S Clinic
Terre Haute, Indiana, United States, 47804
Sponsors and Collaborators
Hoosier Cancer Research Network
Pfizer
Roche Pharma AG
Walther Cancer Institute
Investigators
Study Chair: Elena Gabriela Chiorean, M.D. Hoosier Oncology Group, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Elena Gabriela Chiorean, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00216086     History of Changes
Other Study ID Numbers: HOG GI03-53
Study First Received: September 9, 2005
Last Updated: April 28, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Hoosier Cancer Research Network:
Rectal Cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Capecitabine
Fluorouracil
Irinotecan
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014