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Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00682786
First Posted: May 22, 2008
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
Results First Submitted: July 14, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Rectal Carcinoma
Interventions: Drug: 5FU
Radiation: Radiation
Procedure: Surgery of resectable lesions
Drug: Irinotecan

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment to the study opened on 10/07/2002 and the study closed to enrollment on 10/23/2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

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.


Participant Flow:   Overall Study
    Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4)   Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4)
STARTED   98   37 
COMPLETED   96   34 
NOT COMPLETED   2   3 
Withdrawal by Subject                2                2 
Did not receive irinotecan                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Good Risk (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.

Poor Risk (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.

Total Total of all reporting groups

Baseline Measures
   Good Risk (TYMS*2/*2, *2/*3, *2/*4)   Poor Risk (TYMS*3/*3, *3/*4)   Total 
Overall Participants Analyzed 
[Units: Participants]
 98   37   135 
Age 
[Units: Years]
Median (Full Range)
 55 
 (32 to 85) 
 59 
 (26 to 77) 
 56 
 (26 to 85) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      69  70.4%      24  64.9%      93  68.9% 
Male      29  29.6%      13  35.1%      42  31.1% 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   86   29   115 
African American   10   8   18 
Hispanic   1   0   1 
Asian   1   0   1 
Region of Enrollment 
[Units: Participants]
     
United States   98   37   135 
Thymidylate Synthase Enhancer Region (TSER) genotype 
[Units: Participants]
     
*2/*2   26   0   26 
*2/*3   71   0   71 
*2/*4   1   0   1 
*3/*3   0   35   35 
*3/*4   0   2   2 
Performance status [1] 
[Units: Participants]
     
 63   26   89 
 34   11   45 
 1   0   1 
[1]

Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 Fully active able to carry on all predisease performance without restriction

  1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (light house work/office work)
  2. Ambulatory, capable of all selfcare but unable to carry out any work activities. Up & about more than 50% of waking hours
  3. Capable of limited selfcare, confined to bed/chair more than 50% of waking hours
  4. Completely disabled. Cannot carry on selfcare. Totally confined to bed/chair
  5. Dead
Baseline Stage [1] 
[Units: Participants]
     
Stage IIA (T3, N0, M0)   24   10   34 
Stage IIB (T4, N0, M0)   3   0   3 
Stage IIIA (T1-2, N1, M0)   1   0   1 
Stage IIIB (T3-4, N1, M0)   53   19   72 
Stage IIIC (T-any, N2, M0)   3   3   6 
Stage IV (T-any, N-any, M1)   14   5   19 
[1]
  • T describes how far the primary tumor has grown into the wall of the intestine and whether it has grown into nearby areas.
  • N describes the extent of spread to nearby lymph nodes.
  • M indicates whether the cancer has spread to other organs of the body.

Numbers or letters appear after T, N, and M to provide more details about each of these factors. The numbers 0 through 4 indicate increasing severity. The letter X means "cannot be assessed because the information is not available."

Baseline clinical T stage 
[Units: Participants]
     
T1-2   2   0   2 
T3   77   32   109 
T4   19   5   24 
Baseline clinical N stage 
[Units: Participants]
     
N0   30   11   41 
N1   64   22   86 
N2   4   4   8 
Baseline clinical M stage 
[Units: Participants]
     
M0   84   32   116 
M1   14   5   19 
Clinical staging modality 
[Units: Participants]
     
Endoscopic ultrasound   60   21   81 
CT Scan +/- PET Scan   22   6   28 
MRI   16   10   26 
Tumor distance from anal verge (cm) 
[Units: Participants]
     
<5   33   12   45 
5-10   57   21   78 
>10   8   4   12 
Tumor grade 
[Units: Participants]
     
Well differentiated   8   4   12 
Moderately differentiated   68   25   93 
Poorly differentiated   17   7   24 
Not reported   5   1   6 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Rate of Tumor Downstaging Compared With Historical Controls.   [ Time Frame: 1 year after enrollment ]

2.  Secondary:   Complete Response Rates   [ Time Frame: 1 year after enrollment ]

3.  Secondary:   Define Patient Quality of Life Prior to and Following Neoadjuvant Chemoradiation.   [ Time Frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy ]

4.  Secondary:   Determine Patient Fears and Expectations of Pharmacogenetics.   [ Time Frame: Prior to start of study treatment and 3-6 weeks post completion of radiation therapy ]

5.  Post-Hoc:   Toxicities by Genotype Group (Good Risk Versus Poor Risk)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

6.  Post-Hoc:   Overall Survival   [ Time Frame: 1 year, 2 years, and 3 years ]

7.  Post-Hoc:   Relapse-free Survival   [ Time Frame: 1 year, 2 years, and 3 years ]

8.  Post-Hoc:   Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

9.  Post-Hoc:   Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

10.  Post-Hoc:   Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

11.  Post-Hoc:   Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

12.  Post-Hoc:   Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

13.  Post-Hoc:   Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

14.  Post-Hoc:   Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]

15.  Post-Hoc:   Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group)   [ Time Frame: First day of treatment through 30 days after completion of surgery ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Benjamin R. Tan, M.D.
Organization: Washington University School of Medicine
phone: 314-362-3560
e-mail: btan@dom.wustl.edu



Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00682786     History of Changes
Other Study ID Numbers: 02-0561
First Submitted: April 11, 2008
First Posted: May 22, 2008
Results First Submitted: July 14, 2014
Results First Posted: September 8, 2014
Last Update Posted: October 6, 2017