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Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Primary Purpose

Neoplasm, Rectum

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Total mesorectal excision before 56 days (4-8 weeks)
Total mesorectal excision after 56 days (8-12 weeks)
Sponsored by
Ege University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm, Rectum focused on measuring Locally advanced rectal cancer, Neoadjuvant chemoradiation

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Clinic stage II-III cancer ( T3- T4 tm or/and N(+) disease )
  2. Patients with histologically confirmed adenocarcinoma of the rectum
  3. Tumor distal border located within 15 cm. from anal verge (as measured by rigid rectoscopy)
  4. Standardized total mesorectal excision surgery
  5. Tumor must be clinically resectable with curative intent (R0 resection must be most likely)
  6. Elective operation
  7. The patient must consent to be in the study and the informed consent must be signed

Exclusion Criteria:

  1. Clinic stage I and IV cancer disease
  2. Patients with malignant disease of the rectum other than adenocarcinoma
  3. Recurrent rectal cancer
  4. Emergency cases (Mechanical bowel obstruction, perforation)
  5. Other previous or concurrent malignancies
  6. Any contraindication for radiochemotherapy
  7. Previous chemotherapy or radiotherapy to the pelvis
  8. Tumor has arisen from chronic inflammatory bowel disease or hereditary polyposis disease
  9. American Society of Anesthesiologists Score >3 patients

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Early surgery group

    Late surgery group

    Arm Description

    İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.

    İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.

    Outcomes

    Primary Outcome Measures

    Pathological Complete Response Rate
    Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.

    Secondary Outcome Measures

    Completeness of the Mesorectal Dissection
    Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows: Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin. Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin. High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.
    Tumour Regression Grade
    All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard. Tumor regression grade groups were identified as: Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.
    Surgical Complications
    Morbidity will be assessed according to the classification of Clavien-Dindo as follows: Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included. Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death
    Recurrence
    Both pelvic recurrence and distant metastasis will be assessed.
    Disease-free Survival
    Recurrence free survival
    Overall Survival
    Total survival with or without disease

    Full Information

    First Posted
    September 13, 2017
    Last Updated
    March 22, 2022
    Sponsor
    Ege University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03287843
    Brief Title
    Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
    Official Title
    Effect of Timing of Surgery After Neoadjuvant Chemoradiation on Histopathological Results, Complications, Recurrence and Survivals for Locally Advanced Rectal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2022
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1, 2006 (Actual)
    Primary Completion Date
    January 1, 2017 (Actual)
    Study Completion Date
    January 1, 2022 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Ege University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study aimed to compare the outcomes of early versus late surgical resection in patients who underwent curative total mesorectal excision after neoadjuvant chemoradiation. Half of the participants will undergo surgery before 8 weeks, while the other half will undergo surgery after 8 weeks.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neoplasm, Rectum
    Keywords
    Locally advanced rectal cancer, Neoadjuvant chemoradiation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    350 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Early surgery group
    Arm Type
    Experimental
    Arm Description
    İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.
    Arm Title
    Late surgery group
    Arm Type
    Experimental
    Arm Description
    İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.
    Intervention Type
    Procedure
    Intervention Name(s)
    Total mesorectal excision before 56 days (4-8 weeks)
    Intervention Description
    Low anterior resection or abdominoperineal resection
    Intervention Type
    Procedure
    Intervention Name(s)
    Total mesorectal excision after 56 days (8-12 weeks)
    Intervention Description
    Low anterior resection or abdominoperineal resection
    Primary Outcome Measure Information:
    Title
    Pathological Complete Response Rate
    Description
    Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.
    Time Frame
    2 months
    Secondary Outcome Measure Information:
    Title
    Completeness of the Mesorectal Dissection
    Description
    Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows: Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin. Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin. High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.
    Time Frame
    30 days after surgery
    Title
    Tumour Regression Grade
    Description
    All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard. Tumor regression grade groups were identified as: Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.
    Time Frame
    30 days after surgery
    Title
    Surgical Complications
    Description
    Morbidity will be assessed according to the classification of Clavien-Dindo as follows: Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included. Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death
    Time Frame
    90 days after surgery
    Title
    Recurrence
    Description
    Both pelvic recurrence and distant metastasis will be assessed.
    Time Frame
    5 years after surgery
    Title
    Disease-free Survival
    Description
    Recurrence free survival
    Time Frame
    5 years after surgery
    Title
    Overall Survival
    Description
    Total survival with or without disease
    Time Frame
    5 years after surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Clinic stage II-III cancer ( T3- T4 tm or/and N(+) disease ) Patients with histologically confirmed adenocarcinoma of the rectum Tumor distal border located within 15 cm. from anal verge (as measured by rigid rectoscopy) Standardized total mesorectal excision surgery Tumor must be clinically resectable with curative intent (R0 resection must be most likely) Elective operation The patient must consent to be in the study and the informed consent must be signed Exclusion Criteria: Clinic stage I and IV cancer disease Patients with malignant disease of the rectum other than adenocarcinoma Recurrent rectal cancer Emergency cases (Mechanical bowel obstruction, perforation) Other previous or concurrent malignancies Any contraindication for radiochemotherapy Previous chemotherapy or radiotherapy to the pelvis Tumor has arisen from chronic inflammatory bowel disease or hereditary polyposis disease American Society of Anesthesiologists Score >3 patients
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Z.Erhan Akgun, Proffesor
    Organizational Affiliation
    Ege University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    36254732
    Citation
    Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Doganavsargil B, Ozkok S, Kose T, Karabulut B, Elmas N, Ozutemiz O. Effect of interval between neoadjuvant chemoradiotherapy and surgery on disease recurrence and survival in rectal cancer: long-term results of a randomized clinical trial. BJS Open. 2022 Sep 2;6(5):zrac107. doi: 10.1093/bjsopen/zrac107.
    Results Reference
    derived
    PubMed Identifier
    30155949
    Citation
    Akgun E, Caliskan C, Bozbiyik O, Yoldas T, Sezak M, Ozkok S, Kose T, Karabulut B, Harman M, Ozutemiz O. Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2018 Oct;105(11):1417-1425. doi: 10.1002/bjs.10984. Epub 2018 Aug 29.
    Results Reference
    derived

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    Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

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