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Total Neoadjuvant Induction and Consolidation CapeOX Plus IMRT With Capecitabine for MRI Defined High-risk Rectal Cancer

Primary Purpose

Rectal Cancer

Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Oxaliplatin
Capecitabine
Intensity modulated radiotherapy
Total mesorectal excision
Sponsored by
Peking University Cancer Hospital & Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer focused on measuring Rectal cancer, neoadjuvant, radiotherapy, chemotherapy, toxicity

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years and ≤75 years.
  • ECOG Performance status 0-1.
  • Histologically confirmed diagnosis of adenocarcinoma of the rectum.
  • The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12 cm based on sigmoidoscopy.
  • Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or CRM (+) based on MRI.
  • No evidence of distant metastases.
  • No prior pelvic radiation therapy.
  • No prior chemotherapy or surgery for rectal cancer.
  • No active infections requiring systemic antibiotic treatment.
  • ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN.
  • Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.

Exclusion Criteria:

  • Recurrent rectal cancer.
  • Anticipated unresectable tumor after neoadjuvant treatment.
  • Creatinine level greater than 1.5 times the upper limit of normal.
  • Patients who have received prior pelvic radiotherapy.
  • Patients who are unable to undergo an MRI.
  • Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
  • Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
  • Other Anticancer or Experimental Therapy.
  • Women who are pregnant or breast-feeding.
  • Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.

Sites / Locations

  • Beijing Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TNT

Arm Description

Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.

Outcomes

Primary Outcome Measures

Major adverse events
Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Secondary Outcome Measures

Disease-free survival (DFS)
The 3-year DFS will be defined as the percentage of patients alive without local recurrence or distant metastasis of disease at 3 years measured from the date of the administration of treatment.
Pathological downstaging rate
The pathological result for each patient will be compared with MRI pre-stage and re-stage and downstaging rate will be recorded.
Compliance rate with neoadjuvant treatment schedule
To measure the compliance rate to the total neoadjuvant treatment schedule.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30 (Aaronson et al., 1993). The questionnaire assesses health status and quality of life of cancer patients using 30 items grouped in one global scale, five multi-item functioning scales, three symptom scales and six single symptom items. The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The validity and reliability of the Mandarin versions of the questionnaire have been established.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Colorectal Cancer Module 29 (EORTC QLQ-CR29)
EORTC QLQ-CR29 (Whistance et al., 2009). The questionnaire measures health-related quality of life in patients with colorectal cancer, using 29 items grouped in four functional scale and 18 symptom scale. The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The validity and reliability of the Mandarin versions of the questionnaire have been established.

Full Information

First Posted
August 4, 2016
Last Updated
July 21, 2021
Sponsor
Peking University Cancer Hospital & Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02864849
Brief Title
Total Neoadjuvant Induction and Consolidation CapeOX Plus IMRT With Capecitabine for MRI Defined High-risk Rectal Cancer
Official Title
Total Neoadjuvant Induction and Consolidation CapeOX Plus Neoadjuvant Intensity Modulated Radiotherapy With Concurrent Capecitabine for MRI Defined High-risk Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 2016 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University Cancer Hospital & Institute

4. Oversight

5. Study Description

Brief Summary
This study is designed to test the efficacy and safety of total neoadjuvant induction and consolidation CapeOX plus neoadjuvant intensity modulated radiotherapy with concurrent capecitabine for MRI defined high-risk rectal cancer.
Detailed Description
This phase II trial is studying the efficacy and safety of total neoadjuvant treatment for MRI defined high-risk locally advanced rectal cancer. MRI imaging features as mrT3c/T3d/T4a/T4b, threatening circumferential resection margin, mrN2 disease or extramural vascular invasion are defined as high-risk factor and proved to associated with unfavorable oncological outcome, especially for distant metastasis. Induction and consolidation chemotherapy plus radiation may increase both systemic and local control. Total neoadjuvant treatment schedule also has advantages as improved patient tolerance, early closure of defunctioning ileostomy etc. In this study, patients with MRI defined high-risk rectal cancer will receive 3 cycles induction CapeOX, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and Total mesorectal excision. The induction chemotherapy related G3-4 toxicity occurred in 42% of patients in GCR-3 trial (23% during RT, 19% during induction chemotherapy). It is hypothesized that the neoadjuvant chemotherapy related G3-4 toxicity rate of the present regimen will be lower than 25% (10% during IMRT, 15% during induction/consolidation chemotherapy). A sample size of 67 achieves 80% power to detect a difference (△P =17%, P1=25%, P0=42%) using a one-sided binomial test. (α= 0.05). If the number of G3-4 toxic event is 21 or less, the hypothesis that P1>= 42% is rejected. About 10 % loss to follow-up was anticipated, so an additional eight patients will be recruited. The study requires 75 subjects in all.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
Keywords
Rectal cancer, neoadjuvant, radiotherapy, chemotherapy, toxicity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TNT
Arm Type
Experimental
Arm Description
Patients with MRI defined high-risk rectal cancer will receive chemotherapy before and after chemoradiation, and will not receive adjuvant treatment. This arm is called total neoadjuvant treatment (TNT). The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX (Capecitabine+Oxaliplatin) over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT if no metastasis occurs.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
OXA
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
CAPE
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated radiotherapy
Other Intervention Name(s)
IMRT
Intervention Type
Procedure
Intervention Name(s)
Total mesorectal excision
Other Intervention Name(s)
TME
Primary Outcome Measure Information:
Title
Major adverse events
Description
Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Disease-free survival (DFS)
Description
The 3-year DFS will be defined as the percentage of patients alive without local recurrence or distant metastasis of disease at 3 years measured from the date of the administration of treatment.
Time Frame
3 years
Title
Pathological downstaging rate
Description
The pathological result for each patient will be compared with MRI pre-stage and re-stage and downstaging rate will be recorded.
Time Frame
1 year
Title
Compliance rate with neoadjuvant treatment schedule
Description
To measure the compliance rate to the total neoadjuvant treatment schedule.
Time Frame
1 year
Title
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
Description
EORTC QLQ-C30 (Aaronson et al., 1993). The questionnaire assesses health status and quality of life of cancer patients using 30 items grouped in one global scale, five multi-item functioning scales, three symptom scales and six single symptom items. The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The validity and reliability of the Mandarin versions of the questionnaire have been established.
Time Frame
Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1
Title
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Colorectal Cancer Module 29 (EORTC QLQ-CR29)
Description
EORTC QLQ-CR29 (Whistance et al., 2009). The questionnaire measures health-related quality of life in patients with colorectal cancer, using 29 items grouped in four functional scale and 18 symptom scale. The items are scored on a four-point Likert scale with higher scores indicating a better level of functioning or a higher level of symptoms. The validity and reliability of the Mandarin versions of the questionnaire have been established.
Time Frame
Time0: before neoadjuvant treatment; Time1: at 4 months after the completion of neoadjuvant radiation; Time2: 12 months after Time1; Time3: 24 months after Time1; Time4: 36 months after Time1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years and ≤75 years. ECOG Performance status 0-1. Histologically confirmed diagnosis of adenocarcinoma of the rectum. The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm based on MRI, or ≤12 cm based on sigmoidoscopy. Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or CRM (+) based on MRI. No evidence of distant metastases. No prior pelvic radiation therapy. No prior chemotherapy or surgery for rectal cancer. No active infections requiring systemic antibiotic treatment. ANC > 1.5 cells/mm3, HGB > 10.0 g/dL, PLT > 100,000/mm3, total bilirubin ≤ 1.5 x ULN, AST≤ 3 x ULN, ALT ≤ 3 x ULN. Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study. Exclusion Criteria: Recurrent rectal cancer. Anticipated unresectable tumor after neoadjuvant treatment. Creatinine level greater than 1.5 times the upper limit of normal. Patients who have received prior pelvic radiotherapy. Patients who are unable to undergo an MRI. Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer. Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA. Other Anticancer or Experimental Therapy. Women who are pregnant or breast-feeding. Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China

12. IPD Sharing Statement

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Total Neoadjuvant Induction and Consolidation CapeOX Plus IMRT With Capecitabine for MRI Defined High-risk Rectal Cancer

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