Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Phase 2

Completed

• Conditions: Rectal Carcinoma
• Interventions: Drug: 5FU; Radiation: Radiation; Procedure: Surgery of resectable lesions; Drug: Irinotecan

• Registration Number: NCT00682786
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-10
• Study First Submitted: 2008-04-11
• Study First Submitted QC: 2008-05-16
• Study First Posted: 2008-05-22
• Primary Completion: 2008-12
• Study Completion: 2010-08
• Results First Submitted: 2014-07-14
• Results First Submitted QC: 2014-09-05
• Results First Posted: 2014-09-08
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-07
• Last Update Posted: 2017-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)	5FU	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.
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)	Radiation	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.
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)	Surgery of resectable lesions	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.
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)	5FU	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.
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)	Radiation	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.
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)	Surgery of resectable lesions	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.
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)	Irinotecan	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.

Primary Outcome Measures

Name	Time	Method
Rate of Tumor Downstaging Compared With Historical Controls.	1 year after enrollment	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%.

Secondary Outcome Measures

Name	Time	Method
Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.	Prior to start of study treatment and 3-6 weeks post completion of radiation therapy	The questionnaire is encouraged but not required.
Determine Patient Fears and Expectations of Pharmacogenetics.	Prior to start of study treatment and 3-6 weeks post completion of radiation therapy	The questionnaire is encouraged but not required.
Complete Response Rates	1 year after enrollment	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%.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States