Clinical trial NCT00216086
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Sponsor: Gabi Chiorean, MD
Start date: 2005-05-01; Completion date: 2008-05-01
Enrollment: 22 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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

Arms: arm 1: * 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: intervention 1: Capecitabine intervention 2: Irinotecan intervention 3: EUS intervention 4: Neoadjuvant Chemotherapy intervention 5: Preoperative Radiation intervention 6: Surgery intervention 7: Adjuvant Chemotherapy
Intervention descriptions: intervention 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 intervention 2: Irinotecan 200 mg/m2 IV, day 1 intervention 3: biopsy per EUS intervention 4: * Irinotecan 200 mg/m2 IV, day 1
* Capecitabine 1000 mg/m2 po bid day 1-14; repeat every three weeks for two cycles intervention 5: 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 6: Surgery within 8 weeks following chemoradiotherapy intervention 7: Adjuvant chemotherapy at investigator's discretion

Protocol documents: