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Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

Primary Purpose

Rectal Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
5FU
Radiation
Surgery of resectable lesions
Irinotecan
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Carcinoma focused on measuring rectal, rectum, cancer, carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)

Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)

Arm Description

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 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.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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%.
Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.
The questionnaire is encouraged but not required.
Determine Patient Fears and Expectations of Pharmacogenetics.
The questionnaire is encouraged but not required.

Full Information

First Posted
April 11, 2008
Last Updated
September 7, 2017
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00682786
Brief Title
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Official Title
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Carcinoma
Keywords
rectal, rectum, cancer, carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
135 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)
Arm Type
Experimental
Arm Description
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.
Arm Title
Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
5FU
Other Intervention Name(s)
Fluorouracil, 5-fluorouracil
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Type
Procedure
Intervention Name(s)
Surgery of resectable lesions
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Primary Outcome Measure Information:
Title
Rate of Tumor Downstaging Compared With Historical Controls.
Description
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%.
Time Frame
1 year after enrollment
Secondary Outcome Measure Information:
Title
Complete Response Rates
Description
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%.
Time Frame
1 year after enrollment
Title
Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.
Description
The questionnaire is encouraged but not required.
Time Frame
Prior to start of study treatment and 3-6 weeks post completion of radiation therapy
Title
Determine Patient Fears and Expectations of Pharmacogenetics.
Description
The questionnaire is encouraged but not required.
Time Frame
Prior to start of study treatment and 3-6 weeks post completion of radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Tan, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

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