Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Determine if genotype-directed neoadjuvant chemoradiation, using information from the thymidylate synthase promoter polymorphism, result in a greater degree of tumor downstaging in high risk patients compared to historical controls.

Study Overview

• Status: Completed
• Conditions: Rectal Carcinoma
• Intervention / Treatment: Drug: Irinotecan; Radiation: Radiation; Drug: 5FU; Procedure: Surgery of resectable lesions

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy proven adenocarcinoma of the rectum
• Lesion evaluated by surgeon and found to be resectable
• Stage T3 or T4 disease on radiography or ultrasound
• Karnofsky Performance Status at >60

• Laboratory criteria:

  • Absolute neutrophil count >= 1.5 K
  • Platelets >= 100 K
  • Total Bilirubin <= 2.0;
  • SGOT and Alkaline Phosphatase <= 2 x upper limit of normal
  • Creatinine < 2.0
• Informed consent signed
• Patients with distant metastatic disease will be eligible if they satisfy all other conditions.

Exclusion Criteria:

• Pregnant women, children < 18 years, or patients unable to give informed consent
• Patients with a past history of pelvic radiotherapy.
• Patients with prior malignancy in the past 5 years except: skin cancer or in-situ cervical cancer. However, patients with synchronous adenocarcinomas are eligible provided either (a) the synchronous adenocarcinoma was in a removed pedunculated polyp and did not invade the stalk or (b) the synchronous adenocarcinoma was in a removed polyp that lay within the surgical field (extent of resection would not be changed) or (c) the synchronous adenocarcinoma is smaller than the index rectal cancer and lies completely within the radiation field (clinically favorable second lesion and the extend of radiation and surgery would not be changed).
• Patients with known allergy to 5-fluorouracil or irinotecan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4); Radiation 45 Gy in 25 fractions to the pelvis. 5FU CIVI 225 mg/m2/day by CIVI during radiation Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.	Radiation: Radiation; Drug: 5FU; Other Names: 5-fluorouracil; Fluorouracil; Procedure: Surgery of resectable lesions
Experimental: Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4); Radiation 45 Gy in 25 fractions to the pelvis. 5FU CIVI 225 mg/m2/day by CIVI during radiation Irinotecan 50 mg/m2 IV weekly for 5 doses. Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable.	Drug: Irinotecan; Other Names: Camptosar; Radiation: Radiation; Drug: 5FU; Other Names: 5-fluorouracil; Fluorouracil; Procedure: Surgery of resectable lesions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Tumor Downstaging Compared With Historical Controls.	Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1. Historical studies demonstrate a DS rate of 45%.	1 year after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rates	Complete tumor response is defined as the absence of any viable tumor in the rectum (ypT0). Pathologic complete response (pCR) is defined as the absence of any viable tumor in the rectum or in the perirectal lymph nodes (ypT0N0). pCR rate of historical controls is 8%-14%.	1 year after enrollment
Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.	The questionnaire is encouraged but not required.	Prior to start of study treatment and 3-6 weeks post completion of radiation therapy
Determine Patient Fears and Expectations of Pharmacogenetics.	The questionnaire is encouraged but not required.	Prior to start of study treatment and 3-6 weeks post completion of radiation therapy

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: April 11, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (Estimate): May 22, 2008

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: carcinoma; cancer; rectum; rectal
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Carcinoma; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Irinotecan
• Other Study ID Numbers: 02-0561