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

Rectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00216086
• Other study ID #: HOG GI03-53
• Status: Terminated
• Phase: Phase 2
• First received: September 9, 2005
• Last updated: April 28, 2011
• Start date: January 2005
• Est. completion date: May 2008

Study information

• Verified date: April 2011
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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
• 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
• Surgery
Surgery within 8 weeks following chemoradiotherapy
• Adjuvant Chemotherapy
Adjuvant chemotherapy at investigator's discretion

Locations

Country	Name	City	State
United States	Elkhart Clinic	Elkhart	Indiana
United States	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana
United States	Center for Cancer Care at Goshen Health System	Goshen	Indiana
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Quality Cancer Center (MCGOP)	Indianapolis	Indiana
United States	Medical Consultants, P.C.	Muncie	Indiana
United States	Center for Cancer Care, Inc., P.C.	New Albany	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	AP&S Clinic	Terre Haute	Indiana

Sponsors (4)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Pfizer, Roche Pharma AG, Walther Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	· 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.		36 months	No
Secondary	· 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		36 months	Yes

External Links

•   Hoosier Oncology Group Home Page