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Trial record 43 of 1548 for:    rectal cancer

Preoperative CRT With Temozolomide Plus Capecitabine in Rectal Cancer

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.
 
ClinicalTrials.gov Identifier: NCT01781403
Recruitment Status : Active, not recruiting
First Posted : February 1, 2013
Results First Posted : June 23, 2016
Last Update Posted : February 2, 2018
Sponsor:
Information provided by (Responsible Party):
Tae Won Kim, Asan Medical Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rectal Cancer
Intervention Drug: Temozolomide
Enrollment 22
Recruitment Details Participants were enrolled from 14 May 2013 through 8 May 2014
Pre-assignment Details  
Arm/Group Title Capecitabine 825mg/m^2, Temozolomide 45mg/m^2, Radiotherapy Capecitabine 825mg/m^2, Temozolomide 60mg/m^2, Radiotherapy Capecitabine 825mg/m^2, Temozolomide 75mg/m^2, Radiotherapy
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The total dose of radiotherapy will be 50.4 Gy, with a daily dose of 1.8 Gy administered on 5 days of each week, comprising a total of 45 Gy to the whole pelvis, followed by a 5.4 Gy boost to the primary tumor.

The doses and schedules for capecitabine will be fixed, with only temozolomide being prescribed using a dose-escalation schedule. Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break).

Temozolomide: Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.

The total dose of radiotherapy will be 50.4 Gy, with a daily dose of 1.8 Gy administered on 5 days of each week, comprising a total of 45 Gy to the whole pelvis, followed by a 5.4 Gy boost to the primary tumor.

The doses and schedules for capecitabine will be fixed, with only temozolomide being prescribed using a dose-escalation schedule. Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break).

Temozolomide: Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.

The total dose of radiotherapy will be 50.4 Gy, with a daily dose of 1.8 Gy administered on 5 days of each week, comprising a total of 45 Gy to the whole pelvis, followed by a 5.4 Gy boost to the primary tumor.

The doses and schedules for capecitabine will be fixed, with only temozolomide being prescribed using a dose-escalation schedule. Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break).

Temozolomide: Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.

Period Title: Overall Study
Started 2 2 18
Completed 2 2 18
Not Completed 0 0 0
Arm/Group Title Capecitabine, Temozolomide, Radiotherapy
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The total dose of radiotherapy will be 50.4 Gy, with a daily dose of 1.8 Gy administered on 5 days of each week, comprising a total of 45 Gy to the whole pelvis, followed by a 5.4 Gy boost to the primary tumor.

The doses and schedules for capecitabine will be fixed, with only temozolomide being prescribed using a dose-escalation schedule. Capecitabine and temozolomide will be administered during radiotherapy with drug holidays (weekend break).

Temozolomide: Preoperative chemoradiotherapy with fixed dose of capecitabine and temozolomide, the dose of temozolomide will be escalated for finding MTD and RD.

Overall Number of Baseline Participants 22
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 22 participants
54
(41 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants
Female
7
  31.8%
Male
15
  68.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Korea, Republic of Number Analyzed 22 participants
22
1.Primary Outcome
Title Maximum Tolerated Dose (MTD)
Hide Description The MTD is defined as the maximum dose level in the doses of temozolomide tested with capecitabine and radiation in which the incidence proportion of DLT exceeds 30%.
Time Frame 5-6 weeks during study treatment
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[Not Specified]
Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
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Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 45 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 60 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 75 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Overall Number of Participants Analyzed 2 2 18
Measure Type: Number
Unit of Measure: mg/m^2
0 0 0
2.Primary Outcome
Title Recommended Dose (RD)
Hide Description RD will be defined as one level below the MTD.
Time Frame 5-6 weeks after CRT
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[Not Specified]
Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
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Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 45 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 60 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 75 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Overall Number of Participants Analyzed 2 2 18
Measure Type: Number
Unit of Measure: mg/m^2
0 0 75
3.Secondary Outcome
Title Pathological Complete Response
Hide Description

Pathologic responses and stages were classified according to Dworak’s classification and the 7th edition of the American Joint Committee on Cancer staging system, respectively.

The pathologic complete response (pCR) was defined as the total regression of the primary tumor regardless of regional lymph nodal status (ypT0), with residual fibrotic mass or acellular mucin pools only, thus without detectable tumor cells.

Time Frame at the time of surgery (6-8 weeks after study treatment)
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[Not Specified]
Arm/Group Title Unmethylated MGMT Hypermethylated MGMT
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MGMT methylation specific PCR: unmethlyated
MGMT methylation specific PCR: hypermethylated
Overall Number of Participants Analyzed 6 16
Measure Type: Number
Unit of Measure: participants
1 6
4.Other Pre-specified Outcome
Title Toxicity
Hide Description

Toxicity will be monitored and recorded every week during study treatment (5 or 6 weeks) as following according to the NCI-CTCAE version 4.0

  1. An interval history and physical examination with particular attention to drug-induced side effects along with documentation of the patient’s weight and performance status will be performed on each visit.
  2. CBC with differential count, blood chemistry including calcium, phosphorus, glucose, BUN, creatinine, total protein, albumin, AST, ALT, alkaline phosphatase, total bilirubin, and electrolyte will be performed before next planned treatment.
  3. All relevant information regarding drug dosage, laboratory examinations, and treatment-related toxicities must be recorded before each treatment is given.
  4. Summaries of the frequency and severity of adverse effects are based on the worst episodes recorded.
Time Frame 5-6 weeks during study treatment
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
Hide Arm/Group Description:

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 45 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 60 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 75 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Overall Number of Participants Analyzed 2 2 18
Measure Type: Number
Unit of Measure: events
Any grade 1 adverse event 6 8 60
Any grade 2 adverse event 2 2 17
Any grade 3 adverse event 1 0 3
Any grade 4 adverse event 0 0 0
5.Other Pre-specified Outcome
Title Efficacy
Hide Description

Efficacy: Pathologic major responses = total regression + near total regression.

We will carefully inspect the circumferential resection margin, defining a positive margin as any residual tumor within ≤ 1 mm of the circumferential margin.

Pathologic responses and stages will be classified according to Dworak’s classification1 and the AJCC (American Joint Committee on Cancer) staging system, respectively. In each case, the entire tumor including mesorectal fat will be serially sliced into 4-mm-thick sections and embedded in paraffin.

A pathologic complete response is defined as grade 4 tumor regression; with residual fibrotic mass or acellular mucin pools only, thus without detectable tumor cells

A near total response is defined as grade 3 tumor regression; with very few tumor cells in fibrotic tissue with or without mucous substance.

Time Frame after surgery (6-8 weeks after study treatment)
Outcome Measure Data Not Reported
6.Other Pre-specified Outcome
Title Disease-free Survival
Hide Description [Not Specified]
Time Frame 3-year or 5-year after surgery
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
Hide Arm/Group Description

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 45 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 60 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

Capecitabine was given 825 mg/m^2 twice/day during radiotherapy with drug holidays (weekend breaks).

Temozolomide was given 75 mg/m^2 once/day during radiotherapy with drug holidays (weekend breaks).

All-Cause Mortality
Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/2 (0.00%)      0/2 (0.00%)      0/18 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dose Level 1 Dose Level 2 Dose Level 3/Recommended Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/2 (100.00%)      2/2 (100.00%)      18/18 (100.00%)    
Blood and lymphatic system disorders       
Anemia   2/2 (100.00%)  2 1/2 (50.00%)  1 10/18 (55.56%)  10
Febrile neutropenia   0/2 (0.00%)  0 0/2 (0.00%)  0 0/18 (0.00%)  0
Leukopenia   2/2 (100.00%)  2 0/2 (0.00%)  0 13/18 (72.22%)  13
Neutropenia   2/2 (100.00%)  2 0/2 (0.00%)  0 7/18 (38.89%)  7
Thrombocytopenia   0/2 (0.00%)  0 0/2 (0.00%)  0 4/18 (22.22%)  4
Gastrointestinal disorders       
Anorexia   1/2 (50.00%)  1 1/2 (50.00%)  1 3/18 (16.67%)  3
Constipation   0/2 (0.00%)  0 1/2 (50.00%)  1 6/18 (33.33%)  6
Diarrhea   0/2 (0.00%)  0 1/2 (50.00%)  1 3/18 (16.67%)  3
Nausea   1/2 (50.00%)  1 2/2 (100.00%)  2 14/18 (77.78%)  14
Vomiting   0/2 (0.00%)  0 1/2 (50.00%)  1 5/18 (27.78%)  5
General disorders       
Fatigue   1/2 (50.00%)  1 2/2 (100.00%)  2 3/18 (16.67%)  3
Hand–foot syndrome   0/2 (0.00%)  0 0/2 (0.00%)  0 0/18 (0.00%)  0
Hepatobiliary disorders       
ALT abnormalities   0/2 (0.00%)  0 0/2 (0.00%)  0 7/18 (38.89%)  7
AST abnormalities   0/2 (0.00%)  0 0/2 (0.00%)  0 5/18 (27.78%)  5
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Layout table for Results Point of Contact information
Name/Title: Dr. Tae Won Kim
Organization: Asan Medical Center
Phone: +82-2-3010-3910
EMail: twkimmd@amc.seoul.kr
Layout table for additonal information
Responsible Party: Tae Won Kim, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01781403     History of Changes
Other Study ID Numbers: ML28381
First Submitted: January 21, 2013
First Posted: February 1, 2013
Results First Submitted: May 17, 2016
Results First Posted: June 23, 2016
Last Update Posted: February 2, 2018