Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT00682786
Collaborator
(none)
135
1
2
94
1.4
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
135 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Genotype-directed Neoadjuvant Chemoradiation for Rectal Carcinoma
Study Start Date
:
Oct 1, 2002
Actual Primary Completion Date
:
Dec 1, 2008
Actual Study Completion Date
:
Aug 1, 2010
Arms and Interventions
| 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. |
Drug: 5FU
Other Names:
Radiation: Radiation
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: 5FU
Other Names:
Radiation: Radiation
Procedure: Surgery of resectable lesions
Drug: Irinotecan
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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%.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
Investigators
- Principal Investigator: Benjamin Tan, M.D., Washington University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00682786
Other Study ID Numbers:
- 02-0561
First Posted:
May 22, 2008
Last Update Posted:
Oct 6, 2017
Last Verified:
Sep 1, 2017
Keywords provided by Washington University School of Medicine
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Enrollment to the study opened on 10/07/2002 and the study closed to enrollment on 10/23/2008. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Period Title: Overall Study | ||
| STARTED | 98 | 37 |
| COMPLETED | 96 | 34 |
| NOT COMPLETED | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) | Total |
|---|---|---|---|
| Arm/Group 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. | Total of all reporting groups |
| Overall Participants | 98 | 37 | 135 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
55
|
59
|
56
|
| Sex: Female, Male (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 (participants) [Number] | |||
| White |
86
87.8%
|
29
78.4%
|
115
85.2%
|
| African American |
10
10.2%
|
8
21.6%
|
18
13.3%
|
| Hispanic |
1
1%
|
0
0%
|
1
0.7%
|
| Asian |
1
1%
|
0
0%
|
1
0.7%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
98
100%
|
37
100%
|
135
100%
|
| Thymidylate Synthase Enhancer Region (TSER) genotype (participants) [Number] | |||
| *2/*2 |
26
26.5%
|
0
0%
|
26
19.3%
|
| *2/*3 |
71
72.4%
|
0
0%
|
71
52.6%
|
| *2/*4 |
1
1%
|
0
0%
|
1
0.7%
|
| *3/*3 |
0
0%
|
35
94.6%
|
35
25.9%
|
| *3/*4 |
0
0%
|
2
5.4%
|
2
1.5%
|
| Performance status (participants) [Number] | |||
| 0 |
63
64.3%
|
26
70.3%
|
89
65.9%
|
| 1 |
34
34.7%
|
11
29.7%
|
45
33.3%
|
| 2 |
1
1%
|
0
0%
|
1
0.7%
|
| Baseline Stage (participants) [Number] | |||
| Stage IIA (T3, N0, M0) |
24
24.5%
|
10
27%
|
34
25.2%
|
| Stage IIB (T4, N0, M0) |
3
3.1%
|
0
0%
|
3
2.2%
|
| Stage IIIA (T1-2, N1, M0) |
1
1%
|
0
0%
|
1
0.7%
|
| Stage IIIB (T3-4, N1, M0) |
53
54.1%
|
19
51.4%
|
72
53.3%
|
| Stage IIIC (T-any, N2, M0) |
3
3.1%
|
3
8.1%
|
6
4.4%
|
| Stage IV (T-any, N-any, M1) |
14
14.3%
|
5
13.5%
|
19
14.1%
|
| Baseline clinical T stage (participants) [Number] | |||
| T1-2 |
2
2%
|
0
0%
|
2
1.5%
|
| T3 |
77
78.6%
|
32
86.5%
|
109
80.7%
|
| T4 |
19
19.4%
|
5
13.5%
|
24
17.8%
|
| Baseline clinical N stage (participants) [Number] | |||
| N0 |
30
30.6%
|
11
29.7%
|
41
30.4%
|
| N1 |
64
65.3%
|
22
59.5%
|
86
63.7%
|
| N2 |
4
4.1%
|
4
10.8%
|
8
5.9%
|
| Baseline clinical M stage (participants) [Number] | |||
| M0 |
84
85.7%
|
32
86.5%
|
116
85.9%
|
| M1 |
14
14.3%
|
5
13.5%
|
19
14.1%
|
| Clinical staging modality (participants) [Number] | |||
| Endoscopic ultrasound |
60
61.2%
|
21
56.8%
|
81
60%
|
| CT Scan +/- PET Scan |
22
22.4%
|
6
16.2%
|
28
20.7%
|
| MRI |
16
16.3%
|
10
27%
|
26
19.3%
|
| Tumor distance from anal verge (cm) (participants) [Number] | |||
| <5 |
33
33.7%
|
12
32.4%
|
45
33.3%
|
| 5-10 |
57
58.2%
|
21
56.8%
|
78
57.8%
|
| >10 |
8
8.2%
|
4
10.8%
|
12
8.9%
|
| Tumor grade (participants) [Number] | |||
| Well differentiated |
8
8.2%
|
4
10.8%
|
12
8.9%
|
| Moderately differentiated |
68
69.4%
|
25
67.6%
|
93
68.9%
|
| Poorly differentiated |
17
17.3%
|
7
18.9%
|
24
17.8%
|
| Not reported |
5
5.1%
|
1
2.7%
|
6
4.4%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX 6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician |
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 90 | 31 |
| Number (95% Confidence Interval) [percentage of participants] |
64.4
65.7%
|
64.5
174.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 8 not evaluable in Good Risk arm-(1)death before surgery (1)clinical CR w/o surgery (1)refused surgery (2)not resectable (2)withdrew consent (1)delayed surgery and given FOLFOX 6 not evaluable in Poor Risk arm-(1) death prior to surgery (1)clinical CR no surgery (1)refused surgery (2)withdrew consent (1)not given irinotecan by treating physician |
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 90 | 31 |
| ypT0 |
20
20.4%
|
41.9
113.2%
|
| pCR |
18.9
19.3%
|
35.5
95.9%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The data was not collected for this outcome measure as the questionnaire was encouraged but not required. |
| Arm/Group Title | Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 0 | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The data was not collected for this outcome measure as the questionnaire was encouraged but not required. |
| Arm/Group Title | Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 0 | 0 |
| Title | Toxicities by Genotype Group (Good Risk Versus Poor Risk) |
|---|---|
| Description | Grade 3 to 4 toxicities related to treatment and surgery using CTC Version 2.0. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 96 | 35 |
| Nausea |
0
0%
|
1
2.7%
|
| Vomiting |
0
0%
|
1
2.7%
|
| Diarrhea |
17
17.3%
|
16
43.2%
|
| Dehydration |
3
3.1%
|
7
18.9%
|
| Mucositis |
4
4.1%
|
1
2.7%
|
| GI bleed |
2
2%
|
0
0%
|
| Ileitis |
0
0%
|
1
2.7%
|
| Enteritis |
1
1%
|
0
0%
|
| Dyspnea |
1
1%
|
0
0%
|
| Neutropenia |
0
0%
|
1
2.7%
|
| Anemia |
3
3.1%
|
3
8.1%
|
| Pain |
3
3.1%
|
4
10.8%
|
| Perforation |
2
2%
|
1
2.7%
|
| Pelvic abscess |
0
0%
|
2
5.4%
|
| PPE |
0
0%
|
1
2.7%
|
| Crohn's flare |
1
1%
|
0
0%
|
| Syncope |
2
2%
|
0
0%
|
| Rash |
2
2%
|
0
0%
|
| Fatigue |
1
1%
|
0
0%
|
| Atrial fibrillation |
1
1%
|
0
0%
|
| Infection |
1
1%
|
1
2.7%
|
| Headache |
1
1%
|
0
0%
|
| Small bowel obstruction |
1
1%
|
0
0%
|
| Title | Overall Survival |
|---|---|
| Description | Analyzed using Kaplan-Meier Models. |
| Time Frame | 1 year, 2 years, and 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Two of the patients in the Good Risk arm withdrew consent and are not included. Two of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 96 | 35 |
| 1 year |
96.9
98.9%
|
94.3
254.9%
|
| 2 years |
80.6
82.2%
|
94.3
254.9%
|
| 3 years |
78.2
79.8%
|
83.6
225.9%
|
| Title | Relapse-free Survival |
|---|---|
| Description | Analyzed using Kaplan-Meier Models. |
| Time Frame | 1 year, 2 years, and 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| 14 patients in the Good Risk arm had metastatic rectal cancer at time of enrollment are not included in this analyses. 3 patients in the Poor Risk arm had metastatic rectal disease before surgery and are included in this analyses. 2 of the patients in the Good Risk arm and Poork Risk arm withdrew consent and are not included. |
| Arm/Group Title | Good Risk (TYMS*2/*2, *2/*3, *2/*4) | Poor Risk (TYMS*3/*3, *3/*4) |
|---|---|---|
| Arm/Group 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. |
| Measure Participants | 82 | 32 |
| 1 year |
85.2
86.9%
|
87.0
235.1%
|
| 2 years |
78.3
79.9%
|
80.5
217.6%
|
| 3 years |
73.4
74.9%
|
72.4
195.7%
|
| Title | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. MTHFR gene = methylenetetrahydrofolate reductase (NAD(P)H) |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Good Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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 Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. |
| Measure Participants | 75 | 21 |
| CC (MTHFR 677C>T) |
34
34.7%
|
5
13.5%
|
| CT (MTHFR 677C>T) |
34
34.7%
|
12
32.4%
|
| TT (MTHFR 677C>T) |
7
7.1%
|
4
10.8%
|
| Title | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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. | 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. |
| Measure Participants | 19 | 16 |
| CC (MTHFR 677C>T) |
12
12.2%
|
9
24.3%
|
| CT (MTHFR 677C>T) |
6
6.1%
|
7
18.9%
|
| TT (MTHFR 677C>T) |
1
1%
|
0
0%
|
| Title | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Good Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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 Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. |
| Measure Participants | 75 | 21 |
| AA (MTHFR 1298A>C) |
26
26.5%
|
15
40.5%
|
| AC (MTHFR 1298A>C) |
41
41.8%
|
4
10.8%
|
| CC (MTHFR 1298A>C) |
8
8.2%
|
2
5.4%
|
| Title | Associations Between MTHFR Genotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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. | 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. |
| Measure Participants | 19 | 16 |
| AA (MTHFR 1298A>C) |
9
9.2%
|
8
21.6%
|
| AC (MTHFR 1298A>C) |
9
9.2%
|
6
16.2%
|
| CC (MTHFR 1298A>C) |
1
1%
|
2
5.4%
|
| Title | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Good Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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 Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. |
| Measure Participants | 75 | 21 |
| 677C-1298A |
33
33.7%
|
12
32.4%
|
| 677C-1298C |
49
50%
|
6
16.2%
|
| 677T-1298A |
40
40.8%
|
16
43.2%
|
| Title | Associations Between MTHFR Haplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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. | 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. |
| Measure Participants | 19 | 16 |
| 677C-1298A |
15
15.3%
|
11
29.7%
|
| 677C-1298C |
10
10.2%
|
8
21.6%
|
| 677T-1298A |
7
7.1%
|
7
18.9%
|
| Title | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Good Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Good Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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 Surgery 6-10 weeks after completion of preoperative radiation if disease has become resectable. |
| Measure Participants | 75 | 21 |
| CA-CA |
13
13.3%
|
2
5.4%
|
| CA-CC |
14
14.3%
|
1
2.7%
|
| CA-TA |
6
6.1%
|
9
24.3%
|
| CC-CC |
7
7.1%
|
2
5.4%
|
| CC-TA |
27
27.6%
|
3
8.1%
|
| CC-TC |
1
1%
|
0
0%
|
| TA-TA |
7
7.1%
|
4
10.8%
|
| Title | Associations Between MTHFR Diplotypes and Grade 3-4 Diarrhea and/or Mucositis (Poor Risk Group) |
|---|---|
| Description | Genomic DNA was isolated from whole blood using the Puregene DNA isolation kit. |
| Time Frame | First day of treatment through 30 days after completion of surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| 2 of the patients in the Poor Risk arm withdrew consent and are not included. |
| Arm/Group Title | Without Grade 3-4 Diarrhea and/or Mucositis | With Grade 3-4 Diarrhea and/or Mucositis |
|---|---|---|
| Arm/Group 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. | 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. |
| Measure Participants | 19 | 16 |
| CA-CA |
4
4.1%
|
4
10.8%
|
| CA-CC |
7
7.1%
|
3
8.1%
|
| CA-TA |
4
4.1%
|
4
10.8%
|
| CC-CC |
1
1%
|
2
5.4%
|
| CC-TA |
2
2%
|
3
8.1%
|
| CC-TC |
0
0%
|
0
0%
|
| TA-TA |
1
1%
|
0
0%
|
Adverse Events
| Time Frame | Beginning of treatment through 30 days after the end of surgery. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Two patients in both the "Good Risk Arm" and the "Poor Risk Arm" withdrew consent and are not included. | |||
| Arm/Group Title | Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) | ||
| Arm/Group 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. | ||
All Cause Mortality |
||||
| Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/96 (16.7%) | 12/35 (34.3%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 0/96 (0%) | 1/35 (2.9%) | ||
| Anemia-blood transfusion | 1/96 (1%) | 0/35 (0%) | ||
| Cardiac disorders | ||||
| Myocardial infarction | 1/96 (1%) | 0/35 (0%) | ||
| Atrial fibrillation | 1/96 (1%) | 0/35 (0%) | ||
| Aneurysmal bleed | 0/96 (0%) | 1/35 (2.9%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea/RT enteritis | 7/96 (7.3%) | 7/35 (20%) | ||
| Perforation/abscess/leak fistula | 2/96 (2.1%) | 2/35 (5.7%) | ||
| Gastrointestinal bleed | 1/96 (1%) | 0/35 (0%) | ||
| Crohn's flare | 1/96 (1%) | 0/35 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Hernia repair | 1/96 (1%) | 0/35 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hypoglycemia | 1/96 (1%) | 0/35 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonia | 0/96 (0%) | 1/35 (2.9%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Good Risk (Thymidylate Synthase (TYMS)*2/*2, *2/*3, *2/*4) | Poor Risk (Thymidylate Synthase (TYMS)*3/*3, *3/*4) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 96/96 (100%) | 35/35 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Hemoglobin | 66/96 (68.8%) | 30/35 (85.7%) | ||
| Eye disorders | ||||
| Ocular/vision-eye discomfort | 0/96 (0%) | 1/35 (2.9%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 25/96 (26%) | 19/35 (54.3%) | ||
| Vomiting | 12/96 (12.5%) | 8/35 (22.9%) | ||
| Diarrhea | 72/96 (75%) | 26/35 (74.3%) | ||
| Constipation | 7/96 (7.3%) | 6/35 (17.1%) | ||
| Indigestion/cramping | 13/96 (13.5%) | 10/35 (28.6%) | ||
| Heartburn | 2/96 (2.1%) | 1/35 (2.9%) | ||
| Tenesmus | 13/96 (13.5%) | 1/35 (2.9%) | ||
| Rectal spasms | 1/96 (1%) | 0/35 (0%) | ||
| Flatus | 0/96 (0%) | 1/35 (2.9%) | ||
| Stomatitis/mucositis | 34/96 (35.4%) | 10/35 (28.6%) | ||
| Ileitis/Ileus | 1/96 (1%) | 1/35 (2.9%) | ||
| Bleeding-GI | 17/96 (17.7%) | 4/35 (11.4%) | ||
| Dyspepsia | 0/96 (0%) | 1/35 (2.9%) | ||
| Dry mouth | 1/96 (1%) | 0/35 (0%) | ||
| Pain-rectum | 50/96 (52.1%) | 24/35 (68.6%) | ||
| General disorders | ||||
| Edema | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Chills | 3/96 (3.1%) | 2/35 (5.7%) | ||
| Fever without infection | 2/96 (2.1%) | 3/35 (8.6%) | ||
| Fatigue | 27/96 (28.1%) | 22/35 (62.9%) | ||
| Infections and infestations | ||||
| Infection | 4/96 (4.2%) | 4/35 (11.4%) | ||
| Abscess | 0/96 (0%) | 1/35 (2.9%) | ||
| Investigations | ||||
| Leukocytes (total WBC) | 30/96 (31.3%) | 20/35 (57.1%) | ||
| Platelets | 12/96 (12.5%) | 1/35 (2.9%) | ||
| Neutrophils/granulocytes (ANC/AGC) | 8/96 (8.3%) | 11/35 (31.4%) | ||
| Lymphopenia | 88/96 (91.7%) | 32/35 (91.4%) | ||
| Bilirubin - increased | 26/96 (27.1%) | 12/35 (34.3%) | ||
| SGOT/SGPT - increased | 18/96 (18.8%) | 13/35 (37.1%) | ||
| Alkaline phosphatase - increased | 12/96 (12.5%) | 7/35 (20%) | ||
| BUN - increased | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Creatinine -increased | 19/96 (19.8%) | 6/35 (17.1%) | ||
| Sweats | 4/96 (4.2%) | 0/35 (0%) | ||
| Weight loss | 10/96 (10.4%) | 5/35 (14.3%) | ||
| PT | 5/96 (5.2%) | 2/35 (5.7%) | ||
| PTT | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Defibrillator malfunction | 1/96 (1%) | 0/35 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 6/96 (6.3%) | 6/35 (17.1%) | ||
| Anorexia | 16/96 (16.7%) | 12/35 (34.3%) | ||
| Hyperglycemia | 16/96 (16.7%) | 6/35 (17.1%) | ||
| Hypoalbuminemia | 9/96 (9.4%) | 13/35 (37.1%) | ||
| Hypoglycemia | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Hyponatremia | 9/96 (9.4%) | 8/35 (22.9%) | ||
| Hypernatremia | 1/96 (1%) | 1/35 (2.9%) | ||
| Hypokalemia | 13/96 (13.5%) | 11/35 (31.4%) | ||
| Hyperkalemia | 1/96 (1%) | 0/35 (0%) | ||
| Hypocalcemia | 13/96 (13.5%) | 13/35 (37.1%) | ||
| Hypercalcemia | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Hypoprotenemia | 1/96 (1%) | 0/35 (0%) | ||
| Nervous system disorders | ||||
| Neuropathy - motor | 0/96 (0%) | 2/35 (5.7%) | ||
| Neuropathy-sensory | 1/96 (1%) | 1/35 (2.9%) | ||
| Dizziness | 2/96 (2.1%) | 4/35 (11.4%) | ||
| Syncope | 1/96 (1%) | 0/35 (0%) | ||
| Seizure | 0/96 (0%) | 1/35 (2.9%) | ||
| Tremors | 0/96 (0%) | 1/35 (2.9%) | ||
| Pain-head, headache | 2/96 (2.1%) | 1/35 (2.9%) | ||
| Psychiatric disorders | ||||
| Mood alteration-depression | 0/96 (0%) | 2/35 (5.7%) | ||
| Mood alteration-anxiety | 1/96 (1%) | 2/35 (5.7%) | ||
| Insomnia | 3/96 (3.1%) | 4/35 (11.4%) | ||
| Renal and urinary disorders | ||||
| Dysuria | 14/96 (14.6%) | 4/35 (11.4%) | ||
| Incontinence | 6/96 (6.3%) | 1/35 (2.9%) | ||
| Proteinuria | 3/96 (3.1%) | 2/35 (5.7%) | ||
| Nocturia | 5/96 (5.2%) | 2/35 (5.7%) | ||
| Renal failure | 0/96 (0%) | 1/35 (2.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Hiccoughs | 0/96 (0%) | 1/35 (2.9%) | ||
| Dyspnea | 1/96 (1%) | 2/35 (5.7%) | ||
| Pleural effusion | 1/96 (1%) | 0/35 (0%) | ||
| Cough | 3/96 (3.1%) | 1/35 (2.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin itching/irritation/rash/desquamation | 50/96 (52.1%) | 17/35 (48.6%) | ||
| Skin dryness | 1/96 (1%) | 0/35 (0%) | ||
| Dermatitis | 2/96 (2.1%) | 1/35 (2.9%) | ||
| Erythema/PPE | 20/96 (20.8%) | 4/35 (11.4%) | ||
| Hand-foot syndrome | 7/96 (7.3%) | 2/35 (5.7%) | ||
| Vascular disorders | ||||
| Hypertension | 0/96 (0%) | 3/35 (8.6%) | ||
| Flushing | 1/96 (1%) | 0/35 (0%) | ||
| Deep vein thrombosis | 0/96 (0%) | 1/35 (2.9%) | ||
| Hypotension | 0/96 (0%) | 1/35 (2.9%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Benjamin R. Tan, M.D. |
|---|---|
| Organization | Washington University School of Medicine |
| Phone | 314-362-3560 |
| btan@dom.wustl.edu |
Responsible Party:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00682786
Other Study ID Numbers:
- 02-0561
First Posted:
May 22, 2008
Last Update Posted:
Oct 6, 2017
Last Verified:
Sep 1, 2017