Capecitabine + Irinotecan Followed by Combined Modality Capecitabine and Radiation in Locally Advanced Rectal Cancer
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
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.
Study Overview
Status
Conditions
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Indiana
-
Elkhart, Indiana, United States, 46515
- Elkhart Clinic
-
Fort Wayne, Indiana, United States, 46815
- Fort Wayne Oncology & Hematology, Inc
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Goshen, Indiana, United States, 46527
- Center for Cancer Care at Goshen Health System
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Indianapolis, Indiana, United States, 46202
- Indiana University Cancer Center
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Indianapolis, Indiana, United States, 46202
- Quality Cancer Center (MCGOP)
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Muncie, Indiana, United States, 47303
- Medical Consultants, P.C.
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New Albany, Indiana, United States, 47150
- Center for Cancer Care, Inc., P.C.
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South Bend, Indiana, United States, 46601
- Northern Indiana Cancer Research Consortium
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Terre Haute, Indiana, United States, 47804
- AP&S Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Investigational Treatment
|
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 Names:
Irinotecan 200 mg/m2 IV, day 1
Other Names:
biopsy per EUS
Other Names:
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
Surgery within 8 weeks following chemoradiotherapy
Adjuvant chemotherapy at investigator's discretion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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. |
36 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Local and Distant Disease Recurrence Rates
Time Frame: 36 months
|
To determine the rates of local and distant disease recurrence after treatment.
|
36 months
|
|
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.
|
36 months
|
|
Disease-Free Survival
Time Frame: 36 months
|
The three year rate of Disease-Free Survival
|
36 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Elena Gabriela Chiorean, M.D., Hoosier Oncology Group, LLC
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Capecitabine
- Irinotecan
Other Study ID Numbers
- HOG GI03-53
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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