Clinical trial NCT00216086: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: Rectal Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Roche Pharma AG
name: Walther Cancer Institute
First posted: 2005-09-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Pathological Complete Response (pCR) Rate
timeFrame: 36 months
Secondary outcomes:
measure: Local and Distant Disease Recurrence Rates
timeFrame: 36 months
measure: Rate of Clinical Response
timeFrame: 36 months
measure: Disease-Free Survival
timeFrame: 36 months
Other outcomes:
Locations:
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen Health System
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Quality Cancer Center (MCGOP)
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: New Albany
country: United States
facility: Center for Cancer Care, Inc., P.C.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Terre Haute
country: United States
facility: AP&S Clinic
state: Indiana
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Elena Gabriela Chiorean, M.D.
role: STUDY_CHAIR
References:
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.