Neoplasm, RectumNCT03287843
Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
A study testing Total mesorectal excision before 56 days (4-8 weeks) and Total mesorectal excision after 56 days (8-12 weeks) in people with Neoplasm, Rectum, run by Ege University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Neoplasm, Rectum
- What is being tested?
- Total mesorectal excision before 56 days (4-8 weeks) and Total mesorectal excision after 56 days (8-12 weeks)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2006to 1 Jan 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
About this study
Official title: Effect of Timing of Surgery After Neoadjuvant Chemoradiation on Histopathological Results, Complications, Recurrence and Survivals for Locally Advanced Rectal Cancer
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.
- Conditions
- Neoplasm, Rectum
- Being tested
- Total mesorectal excision before 56 days (4-8 weeks), Total mesorectal excision after 56 days (8-12 weeks)
- Keywords
- Locally advanced rectal cancer, Neoadjuvant chemoradiation
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total mesorectal excision before 56 days (4-8 weeks)Procedure or surgery
Low anterior resection or abdominoperineal resection
Total mesorectal excision after 56 days (8-12 weeks)Procedure or surgery
Low anterior resection or abdominoperineal resection
| Study group | Role | What they receive |
|---|---|---|
| Early surgery group | Experimental | İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Receives: Procedure: Total mesorectal excision before 56 days (4-8 weeks) |
| Late surgery group | Experimental | İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Receives: Procedure: Total mesorectal excision after 56 days (8-12 weeks) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 months
Secondary outcomes (6)
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.
Measured: 30 days after surgery
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.
Measured: 30 days after surgery
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
Measured: 90 days after surgery
Recurrence
Both pelvic recurrence and distant metastasis will be assessed.
Measured: 5 years after surgery
Disease-free Survival
Recurrence free survival
Measured: 5 years after surgery
Overall Survival
Total survival with or without disease
Measured: 5 years after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start1 Jan 2006
- Primary completion1 Jan 2017
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neoplasm, RectumStudies of the same condition, open and under way.
- More trials run by Ege UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ege University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zekeriya Erhan Akgün, Ege University
- Investigators
- Z.Erhan Akgun, Proffesor, Principal investigator, Ege University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287843
- Sponsor's protocol ID
- 17-4.1/13
- Status last verified
- Mar 2022
- First submitted
- 13 Sep 2017
- Last updated
- 31 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36254732Akgun 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.
PubMed 30155949
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Timing of Surgery After Neoadjuvant Chemoradiation on Histopathological Results, Complications, Recurrence and Survivals for Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT03287843
- Acronym / sponsor ID
- 17-4.1/13
- Conditions
- Neoplasm, Rectum
- Keywords
- Locally advanced rectal cancer, Neoadjuvant chemoradiation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Ege UniversityUniversity, hospital or other
- Study start
- 1 Jan 2006 (actual)
- Primary completion
- 1 Jan 2017 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 29 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early surgery group | Experimental | Procedure: Total mesorectal excision before 56 days (4-8 weeks)İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. |
| Late surgery group | Experimental | Procedure: Total mesorectal excision after 56 days (8-12 weeks)İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total mesorectal excision before 56 days (4-8 weeks)Low anterior resection or abdominoperineal resection | Procedure or surgery | Early surgery group |
| Total mesorectal excision after 56 days (8-12 weeks)Low anterior resection or abdominoperineal resection | Procedure or surgery | Late surgery group |
Primary outcome
Pathological Complete Response Rate
Time frame: 2 months
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.
6 secondary outcomes
Completeness of the Mesorectal Dissection
Time frame: 30 days after surgery
Tumour Regression Grade
Time frame: 30 days after surgery
Surgical Complications
Time frame: 90 days after surgery
Recurrence
Time frame: 5 years after surgery
Disease-free Survival
Time frame: 5 years after surgery
Overall Survival
Time frame: 5 years after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36254732Akgun 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.
- Derived from this study: PubMed 30155949Akgun 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Z.Erhan Akgun, Proffesor principal investigator
Ege University
Questions about this trial
What is this clinical trial studying?
A study testing Total mesorectal excision before 56 days (4-8 weeks) and Total mesorectal excision after 56 days (8-12 weeks) in people with Neoplasm, Rectum, run by Ege University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response Rate (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03287843, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2022.