Back to resultsCapecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
Primary Purpose
Rectal Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Irinotecan
EUS
Neoadjuvant Chemotherapy
Preoperative Radiation
Surgery
Adjuvant Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal Cancer
Eligibility 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.
Sites / Locations
- Elkhart Clinic
- Fort Wayne Oncology & Hematology, Inc
- Center for Cancer Care at Goshen Health System
- Indiana University Cancer Center
- Quality Cancer Center (MCGOP)
- Medical Consultants, P.C.
- Center for Cancer Care, Inc., P.C.
- Northern Indiana Cancer Research Consortium
- AP&S Clinic
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Investigational Treatment
Arm Description
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)
Outcomes
Primary Outcome Measures
Pathological Complete Response (pCR) Rate
· 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.
Secondary Outcome Measures
Local and Distant Disease Recurrence Rates
To determine the rates of local and distant disease recurrence after treatment.
Rate of Clinical Response
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
The three year rate of Disease-Free Survival
Full Information
NCT ID
NCT00216086
First Posted
September 9, 2005
Last Updated
April 27, 2016
Sponsor
Gabi Chiorean, MD
Collaborators
Pfizer, Roche Pharma AG, Walther Cancer Institute
1. Study Identification
Unique Protocol Identification Number
NCT00216086
Brief Title
Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Terminated
Why Stopped
Funding withdrawn
Study Start Date
May 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gabi Chiorean, MD
Collaborators
Pfizer, Roche Pharma AG, Walther Cancer Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Investigational Treatment
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
Irinotecan 200 mg/m2 IV, day 1
Intervention Type
Procedure
Intervention Name(s)
EUS
Intervention Description
biopsy per EUS
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant Chemotherapy
Other Intervention Name(s)
Camptosar, Xeloda
Intervention Description
Irinotecan 200 mg/m2 IV, day 1
Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles
Intervention Type
Procedure
Intervention Name(s)
Preoperative Radiation
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Surgery within 8 weeks following chemoradiotherapy
Intervention Type
Procedure
Intervention Name(s)
Adjuvant Chemotherapy
Intervention Description
Adjuvant chemotherapy at investigator's discretion
Primary Outcome Measure Information:
Title
Pathological Complete Response (pCR) Rate
Description
· 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.
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Local and Distant Disease Recurrence Rates
Description
To determine the rates of local and distant disease recurrence after treatment.
Time Frame
36 months
Title
Rate of Clinical Response
Description
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.
Time Frame
36 months
Title
Disease-Free Survival
Description
The three year rate of Disease-Free Survival
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena Gabriela Chiorean, M.D.
Organizational Affiliation
Hoosier Oncology Group, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Elkhart Clinic
City
Elkhart
State/Province
Indiana
ZIP/Postal Code
46515
Country
United States
Facility Name
Fort Wayne Oncology & Hematology, Inc
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46815
Country
United States
Facility Name
Center for Cancer Care at Goshen Health System
City
Goshen
State/Province
Indiana
ZIP/Postal Code
46527
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Quality Cancer Center (MCGOP)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Medical Consultants, P.C.
City
Muncie
State/Province
Indiana
ZIP/Postal Code
47303
Country
United States
Facility Name
Center for Cancer Care, Inc., P.C.
City
New Albany
State/Province
Indiana
ZIP/Postal Code
47150
Country
United States
Facility Name
Northern Indiana Cancer Research Consortium
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
AP&S Clinic
City
Terre Haute
State/Province
Indiana
ZIP/Postal Code
47804
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22610353
Citation
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.
Results Reference
result
Links:
URL
http://hoosieroncologygroup.org/
Description
Hoosier Oncology Group Home Page
Learn more about this trial
Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
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