Rectal CancerPhase 3GRECCAR6NCT01648894
Influence of Lengthening the Interval Between Radiochemotherapy and Surgery on Complete Pathological Response in Rectal Cancer
A Phase 3 study testing Surgery after 11 weeks of delay after chemoradiotherapy. and Surgery after 7 weeks of delay after chemoradiotherapy in people with Rectal Cancer, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
At the end of the neoadjuvant radiochemotherapy, patients are seen by their surgeon to planify the surgery. During this visit, the study will be explained them and their consent obtained. They will then be randomized between the two groups 7 weeks vs. 11 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Surgery after 11 weeks of delay after chemoradiotherapy. and Surgery after 7 weeks of delay after chemoradiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 1 siteFrance
- Study dates
- 25 Oct 2012to 6 May 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age over 18 years, no age limit higher
- Performance status evaluated by the Eastern CooperativeOncology Group (ECOG) score: 0-1,
- Patients with cancer of the middle or lower rectum (lesion located within 10 cm from the dentate line or 12 cm from the anal margin) proved by pathology,
- T3-T4N0, TxN+ on ultrasound-endoscopy and MRI, without secondary localization (M0) on the thoracoabdominal (or chest radiography and abdominal ultrasound)
- Patient who received a protocol between 45-51 Gy of radiotherapy and chemotherapy based on 5-fluorouracil for an average duration of 5 weeks for the management of rectal cancer,
- Curative surgical treatment planned following radiochemotherapy with total mesorectal excision,
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- Free and informed consent signed by the patient,
- Patient affiliated to a social security scheme or beneficiary of such plan(except AME)
- Patient able, according to the investigator, to comply with the requirements of the study.
- The cessation of chemotherapy during radiotherapy does not exclude the patient from the study.
Who cannot join
- Patient with metastasis,
- T1 or T2N0 tumor classified by echo-endoscopy and MRI,
- rectal tumor with lower pole is more than 12 cm from the anal margin or 10 cm from the dentate line,
- Patient did not complete the full protocol of radiotherapy,
- History of tumors (other than basal cell carcinoma and / or carcinoma in situ of the cervix) old less than 10 years
- A patient with impaired or incompetent investigator by not allowing him a good understanding of the requirements of the study,
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- Person under guardianship, persons under guardianship, persons deprived of their liberty by judicial or administrative body, adult subject to legal protection or unable to consent,
- Patient did not complete the full protocole of chemotherapy,
- Pregnant or lactating women.
Trial locations and contacts
1 site in 1 country.
France1 site
Saint-Antoine Hospital - AP-HP, Department of general and digestive surgery
Paris, 75012
About this study
Official title: Randomized Control Trial Comparing the Impact of a Lengthening of the Interval Between the Radiochemotherapy and Surgery (7 Weeks vs. 11 Weeks) on Complete Pathological Response in Rectal Cancer
At the end of the neoadjuvant radiochemotherapy, patients are seen by their surgeon to planify the surgery. During this visit, the study will be explained them and their consent obtained. They will then be randomized between the two groups 7 weeks vs. 11 weeks. Patients were reviewed 15 days before surgery and at 1 and 3 months after surgery. Participation in this study does not change treatment, investigations and consultations usually necessary for management of rectal cancer. The objective is to improve the pathological complete response rate of the rectal cancer.
Read the detailed description
D0: Visit of inclusion and randomization After the end of chemoradiotherapy, the patient is seen in consultation by her / him a surgeon who propose him to participate in the study. At the end of the visit if the patient agrees to participate in it, the investigator at each center will conduct the collection of written consent to the inclusion of the patient. Inclusion will be recorded in the electronic Case Report Form (e-CRF) by the investigator at each center. Randomization (7 or 11 weeks of delay) is performed by the surgeon via the software module CleanWeb randomization.
M1- 1.5 or M2.5 depending of the group randomisation A consultation with the surgeon is held within 15 days (+/- 5 days) of intervention to check the clinical response (tumor regression in rectal tumor distance from the dentate line) and planify surgery. During this visit, the surgeon noted in the e-CRF, clinical findings of the lesion and the results of further investigations.
Not specific exam is requested in the study.
M2 or M3
Surgical procedure:
The anesthesia consultation is planned before the surgery according to the habits of service. Participation in the study does not alter the anesthetic procedures.The patient is admitted the day before surgery in the surgical ward.
During surgery, the operating data are provided on the e-CRF (digital rectal examination under general anesthesia, type of surgery (anterior resection or abdominal-perineal resection), operative time, intraoperative bleeding, macroscopic appearance of the mesorectum, distance from the distal limit of resection). The postoperative complications are noted by the surgeon in the e-CRF during hospitalization (about 10-15 days), and data reporting pathological (Annex 2).
Pathological examination of the specimen of proctectomy is performed according to recommendations for clinical practice using the standard form (Annex 2). The tumor response is evaluated by inclusion of all residual tumor and the response to chemoradiotherapy is graded with the scale of Rödel (Annex 5). A double reading of slides will be made for each patient by two independent pathologists blinded to the randomization group of the patient.
M2 - M5 or M3 - M6 :
Postoperative follow-up :
Following the intervention, no specific consultation is necessary. At follow-up consultations (1 month, 3 months) the surgeon evaluate the postoperative course, planify the stoma closure, noted the potential adverse events and results of morphological examinations (computed tomography, ultrasound, endoscopy) and biological (markers) eventually prescribed.
M6 - M60 :
Cancer surveillance :
Regular follow-up every 3-4 months fo the first two years and every 6 months for the last remaining 3 years (clinical examination, CT-scan and biological marker (CEA))
- Conditions
- Rectal Cancer
- Being tested
- Surgery after 11 weeks of delay after chemoradiotherapy., Surgery after 7 weeks of delay after chemoradiotherapy
- Keywords
- Rectal cancer, radiochemotherapy, complete pathological response
- Medical subject headings
- Rectal Neoplasms, Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgery after 11 weeks of delay after chemoradiotherapy.Procedure or surgery
Surgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 11 weeks of delay after the end of chemoradiotherapy.
Surgery after 7 weeks of delay after chemoradiotherapyProcedure or surgery
Surgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 7 weeks of delay after the end of chemoradiotherapy
| Study group | Role | What they receive |
|---|---|---|
| 11 weeks | Experimental | The cancer surgery is practice 11 weeks after neoadjuvant radio-chemotherapy Receives: Procedure: Surgery after 11 weeks of delay after chemoradiotherapy. |
| 7 weeks | Other | The cancer surgery is practice 7 weeks after neoadjuvant radio-chemotherapy Receives: Procedure: Surgery after 7 weeks of delay after chemoradiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of pathological complete response after pathological examination of surgical specimen defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) in group 7 weeks versus 11 weeks in the group
Measured: 6 month
Secondary outcomes (8)
Rates of clinical response to radio-chemotherapy before surgery, comparison between the two groups (7 versus 11 weeks)
Measured: 6 month
Rate of tumor regression, comparison between the two groups (7 versus 11 weeks)
Measured: 6 month
Rates of operative mortality and morbidity at 90 days, comparison between the two groups (7 versus 11 weeks)
Measured: 6 month
Quality of mesorectum resection, comparison between the two groups (7 versus 11 weeks)
Measured: 6 month
Rate of sphincter preservation, comparison between the two groups (7 versus 11 weeks)
Measured: 6 month
Local and distant recurrence rates, comparison between the two groups (7 versus 11 weeks)
Measured: 5 years
Overall survival and disease-free survival rates, comparison between the two groups (7 versus 11 weeks)
Measured: 5 years
Functional results (LARS score)
LARS questionnaire (Low Anterior Resection Syndrome questionnaire) completed at 24 months and 36 months
Measured: 24 months and 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2012 (estimated)
- Study start25 Oct 2012
- Primary completion22 Oct 2015
- Study completion6 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 265 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jérémie Lefèvre, MD, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01648894
- Sponsor's protocol ID
- P 110125
- Other IDs
- AOM 11304
- Acronym
- GRECCAR6
- Status last verified
- Jul 2022
- First submitted
- 20 Jul 2012
- Last updated
- 25 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E. Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016 Nov 1;34(31):3773-3780. doi: 10.1200/JCO.2016.67.6049.
PubMed 27432930Lefevre JH, Rousseau A, Svrcek M, Parc Y, Simon T, Tiret E; French Research Group of Rectal Cancer Surgery (GRECCAR). A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design. BMC Cancer. 2013 Sep 12;13:417. doi: 10.1186/1471-2407-13-417.
PubMed 24028546
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Control Trial Comparing the Impact of a Lengthening of the Interval Between the Radiochemotherapy and Surgery (7 Weeks vs. 11 Weeks) on Complete Pathological Response in Rectal Cancer
- ClinicalTrials.gov ID
- NCT01648894
- Acronym / sponsor ID
- GRECCAR6 / P 110125
- Conditions
- Rectal Cancer
- Keywords
- Rectal cancer, radiochemotherapy, complete pathological response
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 265 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 25 Oct 2012 (actual)
- Primary completion
- 22 Oct 2015 (actual)
- Study completion
- 6 May 2020 (actual)
- First posted
- 24 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
At the end of the neoadjuvant radiochemotherapy, patients are seen by their surgeon to planify the surgery. During this visit, the study will be explained them and their consent obtained. They will then be randomized between the two groups 7 weeks vs. 11 weeks. Patients were reviewed 15 days before surgery and at 1 and 3 months after surgery. Participation in this study does not change treatment, investigations and consultations usually necessary for management of rectal cancer. The objective is to improve the pathological complete response rate of the rectal cancer.
Detailed description
D0: Visit of inclusion and randomization After the end of chemoradiotherapy, the patient is seen in consultation by her / him a surgeon who propose him to participate in the study. At the end of the visit if the patient agrees to participate in it, the investigator at each center will conduct the collection of written consent to the inclusion of the patient. Inclusion will be recorded in the electronic Case Report Form (e-CRF) by the investigator at each center. Randomization (7 or 11 weeks of delay) is performed by the surgeon via the software module CleanWeb randomization.
M1- 1.5 or M2.5 depending of the group randomisation A consultation with the surgeon is held within 15 days (+/- 5 days) of intervention to check the clinical response (tumor regression in rectal tumor distance from the dentate line) and planify surgery. During this visit, the surgeon noted in the e-CRF, clinical findings of the lesion and the results of further investigations.
Not specific exam is requested in the study.
M2 or M3
Surgical procedure:
The anesthesia consultation is planned before the surgery according to the habits of service. Participation in the study does not alter the anesthetic procedures.The patient is admitted the day before surgery in the surgical ward.
During surgery, the operating data are provided on the e-CRF (digital rectal examination under general anesthesia, type of surgery (anterior resection or abdominal-perineal resection), operative time, intraoperative bleeding, macroscopic appearance of the mesorectum, distance from the distal limit of resection). The postoperative complications are noted by the surgeon in the e-CRF during hospitalization (about 10-15 days), and data reporting pathological (Annex 2).
Pathological examination of the specimen of proctectomy is performed according to recommendations for clinical practice using the standard form (Annex 2). The tumor response is evaluated by inclusion of all residual tumor and the response to chemoradiotherapy is graded with the scale of Rödel (Annex 5). A double reading of slides will be made for each patient by two independent pathologists blinded to the randomization group of the patient.
M2 - M5 or M3 - M6 :
Postoperative follow-up :
Following the intervention, no specific consultation is necessary. At follow-up consultations (1 month, 3 months) the surgeon evaluate the postoperative course, planify the stoma closure, noted the potential adverse events and results of morphological examinations (computed tomography, ultrasound, endoscopy) and biological (markers) eventually prescribed.
M6 - M60 :
Cancer surveillance :
Regular follow-up every 3-4 months fo the first two years and every 6 months for the last remaining 3 years (clinical examination, CT-scan and biological marker (CEA))
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 11 weeks | Experimental | Procedure: Surgery after 11 weeks of delay after chemoradiotherapy.The cancer surgery is practice 11 weeks after neoadjuvant radio-chemotherapy |
| 7 weeks | Other | Procedure: Surgery after 7 weeks of delay after chemoradiotherapyThe cancer surgery is practice 7 weeks after neoadjuvant radio-chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- age over 18 years, no age limit higher
- Performance status evaluated by the Eastern CooperativeOncology Group (ECOG) score: 0-1,
- Patients with cancer of the middle or lower rectum (lesion located within 10 cm from the dentate line or 12 cm from the anal margin) proved by pathology,
- T3-T4N0, TxN+ on ultrasound-endoscopy and MRI, without secondary localization (M0) on the thoracoabdominal (or chest radiography and abdominal ultrasound)
- Patient who received a protocol between 45-51 Gy of radiotherapy and chemotherapy based on 5-fluorouracil for an average duration of 5 weeks for the management of rectal cancer,
Key exclusion criteria (9 listed)
- Patient with metastasis,
- T1 or T2N0 tumor classified by echo-endoscopy and MRI,
- rectal tumor with lower pole is more than 12 cm from the anal margin or 10 cm from the dentate line,
- Patient did not complete the full protocol of radiotherapy,
- History of tumors (other than basal cell carcinoma and / or carcinoma in situ of the cervix) old less than 10 years
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 |
|---|---|---|
| Surgery after 11 weeks of delay after chemoradiotherapy.Surgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 11 weeks of delay after the end of chemoradiotherapy. | Procedure or surgery | 11 weeks |
| Surgery after 7 weeks of delay after chemoradiotherapySurgery consists carcinological resection of the rectal cancer with total excision of the mesorectum after 7 weeks of delay after the end of chemoradiotherapy | Procedure or surgery | 7 weeks |
Primary outcome
Percentage of pathological complete response after pathological examination of surgical specimen defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) in group 7 weeks versus 11 weeks in the group
Time frame: 6 month
8 secondary outcomes
Rates of clinical response to radio-chemotherapy before surgery, comparison between the two groups (7 versus 11 weeks)
Time frame: 6 month
Rate of tumor regression, comparison between the two groups (7 versus 11 weeks)
Time frame: 6 month
Rates of operative mortality and morbidity at 90 days, comparison between the two groups (7 versus 11 weeks)
Time frame: 6 month
Quality of mesorectum resection, comparison between the two groups (7 versus 11 weeks)
Time frame: 6 month
Rate of sphincter preservation, comparison between the two groups (7 versus 11 weeks)
Time frame: 6 month
Local and distant recurrence rates, comparison between the two groups (7 versus 11 weeks)
Time frame: 5 years
Overall survival and disease-free survival rates, comparison between the two groups (7 versus 11 weeks)
Time frame: 5 years
Functional results (LARS score)
Time frame: 24 months and 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2022.
- Derived from this study: PubMed 27432930Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E. Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016 Nov 1;34(31):3773-3780. doi: 10.1200/JCO.2016.67.6049.
- Derived from this study: PubMed 24028546Lefevre JH, Rousseau A, Svrcek M, Parc Y, Simon T, Tiret E; French Research Group of Rectal Cancer Surgery (GRECCAR). A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design. BMC Cancer. 2013 Sep 12;13:417. doi: 10.1186/1471-2407-13-417.
- Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6)Link provided by the sponsor.
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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.
Jérémie Lefèvre, MD principal investigator
Assistance Publique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Surgery after 11 weeks of delay after chemoradiotherapy. and Surgery after 7 weeks of delay after chemoradiotherapy in people with Rectal Cancer, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 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 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of pathological complete response after pathological examination of surgical specimen defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) in group 7 weeks versus 11 weeks in the group (time frame: 6 month). 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 NCT01648894, 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 25 Jul 2022.