Colorectal NeoplasmPhase 3PSSRNCT02121405
Randomized Trial of Primary Surgery Followed Selective Radiochemotherapy for Rectal Cancer With MRI Negative CRM
A Phase 3 study testing Rectectomy, Radiotherapy and Capecitabine in people with Colorectal Neoplasm and Effects of Radiation Therapy, run by Zhejiang University at 7 sites in China.
Trial summary
The purpose of this study is to determine whether primary radiotherapy can be omitted for the locally advanced rectal cancer with Magnetic Resonance Imaging (MRI) negative circumferential margin. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasm, Effects of Radiation Therapy, Effects of Chemotherapy
- What is being tested?
- Rectectomy, Radiotherapy and Capecitabine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 7 sitesChina
- Study dates
- Oct 2015to Feb 2026
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Rectal adenocarcinoma or mucinous adenocarcinoma that is 6-12 cm from the anal verge.
- MRI scan confirmed cT3N0 or cT4aN0 or cT1-4aN+ mid rectal cancer (6-12cm from the anal verge).
- MRI scan confirmed more than 1 mm circumferential margin.
- Age 18-75 years old.
- Without distant metastasis.
Who cannot join
- Malignant history.
- Contraindications of MRI scan.
- Contraindications of radiotherapy.
- Contraindications of chemotherapy.
- Pregnancy.
- Multidisciplinary team thinks that the patient is unsuitable to take part in research (For example, there are obvious regional lymph nodes involved in low rectal cancer patients who are thought with high risk of recurrence).
- Refuse to take part in research.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
China7 sites
Union Hospital Fujian Medical University
Fuzhou, Fujian, 350001
The First Affiliated Hospital of College of Medicine Zhejiang University
Hangzhou, Zhejiang, 310003
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Jinhua People's Hospital
Jinhua, Zhejiang, 321000
Zhongshan Hospital Fudan University
Shanghai, Shanghai Municipality, 200032
Liaoning Cancer Hospital
Shenyang, Liaoning, 110042
Yuyao People's Hospital
Yuyao, Zhejiang, 315400
About this study
Official title: Randomized Trial of Primary Surgery Followed Selective Radiochemotherapy Versus Conventional Preoperative Radiochemotherapy for Locally Advanced Rectal Cancer With MRI Negative Circumferential Margin
The purpose of this study is to determine whether primary radiotherapy can be omitted for the locally advanced rectal cancer with Magnetic Resonance Imaging (MRI) negative circumferential margin.
Read the detailed description
The preoperative radiochemotherapy with fluorouracil followed surgery is the standard therapy for patients with locally advanced rectal cancer. However, the necessity of radiotherapy has been questioned for a long time especially for patients with enough circumferential margins. Moreover, indiscriminate radiotherapy will result Irreversible ovarian dysfunction for female. In the past decade, there were two major progresses for colorectal cancer. Firstly, oxaliplatin with fluorouracil has become the standard adjuvant chemotherapy for advanced colon cancer. Oxaliplatin improved the survival of colon cancer patients than single fluorouracil. Our experience showed that oxaliplatin with fluorouracil could improve the prognosis of rectal cancer without radiotherapy. It has been proven that oxaliplatin should not add to radiotherapy for rectal cancer. However, whether oxaliplatin can replace radiotherapy for certain rectal cancer patients is still unknown. Secondly, Magnetic Resonance Imaging (MRI) has been proven that can predict the circumferential margin status for rectal cancer. Now, preoperative MRI scan can recognize the rectal cancer patients with low recurrence risk. The radiotherapy may be omitted to the patients with low recurrence risk. This study is a randomized controlled trial to compare the 3-year disease-free survival (DFS) differences of group of experiment (the patients receive primary surgery followed selective radiochemotherapy) and group of control (the patients receive indiscriminate preoperative radiochemotherapy followed surgery) for locally advanced rectal cancer with negative MRI circumferential margin.
- Being tested
- Rectectomy, Radiotherapy, Capecitabine, Oxaliplatin
- Medical subject headings
- Colorectal Neoplasms, Radiation Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RectectomyProcedure or surgery
Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).
RadiotherapyRadiation
45-50 Gy in 25-28 fractions to the pelvis. After 45 Gy a tumor bed boost with a 2 cm margin of 5.4 Gy in 3 fractions for preoperative cancers or 5.4-9.0 Gy in 3-5 fractions for postoperative cancers could be considered. Radiotherapy is used only for patients with pathological confirmed positive circumferential margin in Group primary surgery. Radiotherapy is used to all of the patients in Group preoperative radiochemotherapy.
CapecitabineDrug
Also called Xeloda
Capecitabine 825 mg/m2 twice daily 5 or 7 days/week with concurrent radiotherapy in Group primary surgery and Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 weeks after preoperative radiochemotherapy in Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 months postoperative therapy for a part of stage II patients in Group of primary surgery. Capecitabine 1000 mg/m2 twice daily 1-14 every 3 weeks with oxaliplatin day 1 to a total of 6 months postoperative therapy for stage III patients in Group of primary surgery.
OxaliplatinDrug
Also called Eloxatin
Oxaliplatin 130 mg/m2 over 2 hours, day 1, with capecitabine every 3 weeks. Repeat every 3 weeks to total of 6 months postoperative therapy.
| Study group | Role | What they receive |
|---|---|---|
| Primary surgery | Experimental | The patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy. Receives: Procedure: Rectectomy; Radiation: Radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin |
| Preoperative radiochemotherapy | Active comparator | All of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision. Receives: Procedure: Rectectomy; Radiation: Radiotherapy; Drug: Capecitabine; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Measured: Three years from the date of randomization
Secondary outcomes (3)
The rate of positive circumferential resection margin
Measured: 1 day of postoperative pathological examination.
Quality of life by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C(core) 30 and QLQ-CR(colorectal) 29 forms
Measured: Baseline before any treatment,3 months post operation, 1 year post operation
Overall survival
Measured: Five years from the date of randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2014 (estimated)
- Study startOct 2015
- Primary completionFeb 2024 (estimated)
- Study completionFeb 2026 (estimated)
Why it stopped: DSMB stopped this trial due to the difference of 3-year DFS's rate between two groups more than 5% at the interim analysis in July 2021.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmStudies of the same condition, open and under way.
- More trials run by Zhejiang 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ding Ke-Feng, Zhejiang University
- Investigators
- Ke-Feng Ding, M.D., Principal investigator, The Second Affiliated Hospital Zhejiang University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02121405
- Sponsor's protocol ID
- CRCCZ-R01
- Acronym
- PSSR
- Status last verified
- May 2022
- First submitted
- 21 Apr 2014
- Last updated
- 11 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li M, Sun H, Yang W, Luo J, Lin H, Zhou T, Gong H, Zhao D, Niu Z, Wang Z, Liu B, Yi Y, Huang W, Li B. A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer. Int J Radiat Oncol Biol Phys. 2024 Jul 1;119(3):896-901. doi: 10.1016/j.ijrobp.2023.12.033. Epub 2024 Jan 4.
PubMed 38181839
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Primary Surgery Followed Selective Radiochemotherapy Versus Conventional Preoperative Radiochemotherapy for Locally Advanced Rectal Cancer With MRI Negative Circumferential Margin
- ClinicalTrials.gov ID
- NCT02121405
- Acronym / sponsor ID
- PSSR / CRCCZ-R01
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: DSMB stopped this trial due to the difference of 3-year DFS's rate between two groups more than 5% at the interim analysis in July 2021.
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- Feb 2024 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 23 Apr 2014 (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.
The purpose of this study is to determine whether primary radiotherapy can be omitted for the locally advanced rectal cancer with Magnetic Resonance Imaging (MRI) negative circumferential margin.
Detailed description
The preoperative radiochemotherapy with fluorouracil followed surgery is the standard therapy for patients with locally advanced rectal cancer. However, the necessity of radiotherapy has been questioned for a long time especially for patients with enough circumferential margins. Moreover, indiscriminate radiotherapy will result Irreversible ovarian dysfunction for female. In the past decade, there were two major progresses for colorectal cancer. Firstly, oxaliplatin with fluorouracil has become the standard adjuvant chemotherapy for advanced colon cancer. Oxaliplatin improved the survival of colon cancer patients than single fluorouracil. Our experience showed that oxaliplatin with fluorouracil could improve the prognosis of rectal cancer without radiotherapy. It has been proven that oxaliplatin should not add to radiotherapy for rectal cancer. However, whether oxaliplatin can replace radiotherapy for certain rectal cancer patients is still unknown. Secondly, Magnetic Resonance Imaging (MRI) has been proven that can predict the circumferential margin status for rectal cancer. Now, preoperative MRI scan can recognize the rectal cancer patients with low recurrence risk. The radiotherapy may be omitted to the patients with low recurrence risk. This study is a randomized controlled trial to compare the 3-year disease-free survival (DFS) differences of group of experiment (the patients receive primary surgery followed selective radiochemotherapy) and group of control (the patients receive indiscriminate preoperative radiochemotherapy followed surgery) for locally advanced rectal cancer with negative MRI circumferential margin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary surgery | Experimental | Procedure: Rectectomy, Radiation: Radiotherapy, Drug: Capecitabine, Drug: OxaliplatinThe patients receive primary rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. To patients with pathological confirmed positive circumferential margin (CRM), postoperative concurrent radiochemotherapy is required that starts in 3 months post operation with capecitabine. Capecitabine and Oxaliplatin (CapeOx) chemotherapy starts in 4 weeks post operation to total of 6 cycles/18 weeks. To patients with pathological confirmed negative CRM, radiotherapy is omitted. The stage III patients receive 8 cycles/6 months CapeOx chemotherapy. The stage II patients with low microsatellite instability (MSI) receive 8 cycles/6 months Capecitabine chemotherapy. The stage II patients with high MSI and stage I patients do not receive adjuvant therapy. |
| Preoperative radiochemotherapy | Active comparator | Procedure: Rectectomy, Radiation: Radiotherapy, Drug: Capecitabine, Drug: OxaliplatinAll of the patients receive conventional concurrent radiochemotherapy with capecitabine for 5 weeks. Then all of the patients receive 2 cycles/6 weeks capecitabine ± Oxaliplatin chemotherapy. Patients receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with total mesorectal excision 8 weeks post radiotherapy. All of the patients receive 5 cycles/15 weeks capecitabine ± Oxaliplatin adjuvant chemotherapy. The use of Oxaliplatin depends on the doctor's decision. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Rectal adenocarcinoma or mucinous adenocarcinoma that is 6-12 cm from the anal verge.
- MRI scan confirmed cT3N0 or cT4aN0 or cT1-4aN+ mid rectal cancer (6-12cm from the anal verge).
- MRI scan confirmed more than 1 mm circumferential margin.
- Age 18-75 years old.
- Without distant metastasis.
Key exclusion criteria (7 listed)
- Malignant history.
- Contraindications of MRI scan.
- Contraindications of radiotherapy.
- Contraindications of chemotherapy.
- Pregnancy.
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 |
|---|---|---|
| RectectomyInclude anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME). | Procedure or surgery | Preoperative radiochemotherapy, Primary surgery |
| Radiotherapy45-50 Gy in 25-28 fractions to the pelvis. After 45 Gy a tumor bed boost with a 2 cm margin of 5.4 Gy in 3 fractions for preoperative cancers or 5.4-9.0 Gy in 3-5 fractions for postoperative cancers could be considered. Radiotherapy is used only for patients with pathological confirmed positive circumferential margin in Group primary surgery. Radiotherapy is used to all of the patients in Group preoperative radiochemotherapy. | Radiation | Preoperative radiochemotherapy, Primary surgery |
| CapecitabineAlso: XelodaCapecitabine 825 mg/m2 twice daily 5 or 7 days/week with concurrent radiotherapy in Group primary surgery and Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 weeks after preoperative radiochemotherapy in Group preoperative radiochemotherapy. Capecitabine 1250 mg/m2 twice daily 1-14 every 3 weeks to a total of 6 months postoperative therapy for a part of stage II patients in Group of primary surgery. Capecitabine 1000 mg/m2 twice daily 1-14 every 3 weeks with oxaliplatin day 1 to a total of 6 months postoperative therapy for stage III patients in Group of primary surgery. | Drug | Preoperative radiochemotherapy, Primary surgery |
| OxaliplatinAlso: EloxatinOxaliplatin 130 mg/m2 over 2 hours, day 1, with capecitabine every 3 weeks. Repeat every 3 weeks to total of 6 months postoperative therapy. | Drug | Preoperative radiochemotherapy, Primary surgery |
Primary outcome
Disease-free survival
Time frame: Three years from the date of randomization
3 secondary outcomes
The rate of positive circumferential resection margin
Time frame: 1 day of postoperative pathological examination.
Quality of life by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C(core) 30 and QLQ-CR(colorectal) 29 forms
Time frame: Baseline before any treatment,3 months post operation, 1 year post operation
Overall survival
Time frame: Five years from the date of randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2022.
- Derived from this study: PubMed 38181839Li M, Sun H, Yang W, Luo J, Lin H, Zhou T, Gong H, Zhao D, Niu Z, Wang Z, Liu B, Yi Y, Huang W, Li B. A Phase 1b Clinical Trial of Neoadjuvant Radio-immunotherapy for Esophageal Squamous Cell Cancer. Int J Radiat Oncol Biol Phys. 2024 Jul 1;119(3):896-901. doi: 10.1016/j.ijrobp.2023.12.033. Epub 2024 Jan 4.
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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.
Ke-Feng Ding, M.D. principal investigator
The Second Affiliated Hospital Zhejiang University Medical School
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rectectomy, Radiotherapy and Capecitabine in people with Colorectal Neoplasm and Effects of Radiation Therapy, run by Zhejiang University at 7 sites in China.
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 5 inclusion and 7 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: paused, as of the sponsor's last update on 11 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. 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?
Results are not available in the source record.
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?
Disease-free survival (time frame: Three years from the date of randomization). 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 NCT02121405, which also lists 1 linked publication.
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 11 May 2022.