Rectal CancerPhase 3NCT03975049
Triplet Combination or Doublet Regimen Versus Chemoradiation as Neoadjuvant Therapy for Locally Advanced Rectal Cancer
A Phase 3 study testing Chemoradiation, FOLFOXIRI Protocol and Folfox Protocol in people with Rectal Cancer and Chemotherapy Effect, run by Sixth Affiliated Hospital, Sun Yat-sen University.
Trial summary
Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer. Local irradiation significantly increases surgical complications and impairs quality of life. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer, Chemotherapy Effect
- What is being tested?
- Chemoradiation, FOLFOXIRI Protocol and Folfox Protocol
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 933 participants
- Where
- No sites listed yet
- Study dates
- Aug 2019to Jul 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- 1）Age: 18 to 75 years old;
- 2）Histological diagnosis of rectal adenocarcinoma;
- 3）Distance form anal margin ≤ 12cm: cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT, estimated possible for R0 resection;
- 4）There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
- 5）Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
- 6）ECOG Performance Status :0-1
- 7）Life expectancy: more than 3 years;
- 8）sufficient bone marrow, liver and kidney function.
Who cannot join
- 1）Arrhythmia requires treatment with antiarrhythmia (except for beta-blockers or digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the last 6 months) or congestive heart failure exceeding NYHA class II;
- 2）Severe hypertension with poor control;
- 3）History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
- 4）Other active serious infections according to NCI-CTC version 4.0;
- 5）There is preoperative evidence for distant metastasis outside pelvis;
- 6）Cachexia and organ function decompensation
Show all 14Show fewer
- 7）History of pelvic or abdominal radiotherapy;
- 8）Multiple primary cancer;
- 9）Patients with epilepcy requiring treatment ( steroids or antiepileptic treatment);
- 10）History of other malignant tumors within 5 years, except for cured cervical carcinoma in situ or skin basal cell carcinoma;
- 11）Drug abuse and medical, psychological or social conditions interfering patient participation in research or the evaluation of research results;
- 12）Any allergy to clinical research drugs or any drugs associated with this study;
- 13）Any unstable condition or condition that may endanger safety and compliance of patients;
- 14）Pregnancy or the lactating female without adequate contraception.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Prospectively Randomized Phase III Trial Comparing Short-term mFOLFOXIRI, Long-term mFOLFOX6 and Traditional Chemoradiation as Preoperative Neoadjuvant Therapy for Locally Advanced Rectal Cancer
Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer.
Local irradiation significantly increases surgical complications and impairs quality of life.
Combination chemotherapy alone seems promising and provides similar benefit to chemoradiation as neoadjuvant therapy.
Early administration of systemic therapy is also proved beneficial for long-term survival.
The purpose of this study is to compare the efficacy of chemotherapy alone with short-term modified FOLFOXIRI or long-term mFOLFOX with standard chemoradiation as neoadjuvant therapy for locally advanced rectal cancer.
Read the detailed description
Patients with cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT scan will be randomized to the following three groups:
Group A: Traditional chemoradiation.
Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.
At the end of chemoradiation, patients will receive an evaluation with MR and CT scan.
If the efficacy is defined as CR, PR or SD, the TME will be performed in 6-8 weeks since the last irradiation.
If the disease progress with the possibility of R0 resection, the operation will be given soon.
If the tumor progress to impossible for R0 resection, the salvage chemotherapy will be given accordingly.
Adjuvant chemotherapy of 6-8 cycles of mFOLFOX will be administered 3-4 weeks after R0 resection.
Group B: Short-term mFOLFOXIRI.
Oxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended.
Patients are planned to receive 4 cycles of mFOLFOXIRI regimen preoperatively and postoperatively, respectively.
Before operation, efficacy evaluations will be performed every two cycles by CT and MR scan.
If the evaluation is defined as no progression without severe toxicity, the next 2 cycles will be given.
If the primary lesion progress without distant metastasis, patients will be assigned to group A.
If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.
Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.
Group C: Long-term mFOLFOX.
Oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days.
Patients are planned to receive 8-9 cycles of mFOLFOX regimen preoperatively and 3-4 cycles postoperatively.
Efficacy evaluations will be performed every three cycles by CT and MR scan before TME.
If the evaluation is defined as no progression without severe toxicity, the next 3 cycles of mFOLFOX will be given with the maximum of 9 cyces.
If the primary lesion progress without distant metastasis, patients will be assigned to group A.
If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.
Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.
- Conditions
- Rectal Cancer, Chemotherapy Effect
- Being tested
- Chemoradiation, FOLFOXIRI Protocol, Folfox Protocol
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChemoradiationRadiation
Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.
FOLFOXIRI ProtocolDrug
Oxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended.
Folfox ProtocolDrug
Oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| 5-Fu + RT | Active comparator | 5Fu + RT for five weeks --- 6-8 weeks of interval --- TME --- mFOLFOX * 6-8 Receives: Radiation: Chemoradiation |
| mFOLFOXIRI | Experimental | mFOLFOXIRI * 4 --- TME --- mFOLFOXIRI * 4 Receives: Drug: FOLFOXIRI Protocol |
| mFOLFOX | Experimental | mFOLFOX * 9 --- TME --- mFOLFOX * 3 Receives: Drug: Folfox Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
The interval from randomization to local recurrence, distant metastasis, death or the last follow-up.
Measured: 3 years
Secondary outcomes (4)
Recurrence-free survival
The interval from randomization to local recurrence, death or the last follow-up.
Measured: 3 years
Metastasis-free survival
The interval from randomization to distant metastasis, death or the last follow-up.
Measured: 3 years
Surgical complication
Surgical complication including anastomotic leakage, anastomotic stricture, intestinal obstruction, postoperative pelvic bleeding and poor wound healing.
Measured: 3 years
Treatment related quality of life
EORTC QOL questionaire
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2019
- Study startAug 2019 (estimated)
- Primary completionJul 2024 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Sixth Affiliated Hospital, Sun Yat-sen 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
- 933 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ping Lan, MD, Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03975049
- Sponsor's protocol ID
- SAHMO201
- Status last verified
- Jun 2019
- First submitted
- 22 May 2019
- Last updated
- 5 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospectively Randomized Phase III Trial Comparing Short-term mFOLFOXIRI, Long-term mFOLFOX6 and Traditional Chemoradiation as Preoperative Neoadjuvant Therapy for Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT03975049
- Acronym / sponsor ID
- SAHMO201
- Conditions
- Rectal Cancer, Chemotherapy Effect
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 933 participants (estimated)
- Lead sponsor
- Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- Aug 2019 (estimated)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 5 Jun 2019 (actual)
- 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.
Preoperative radiation with single agent chemotherapy as sensitizer is the standard care of locally advanced rectal cancer.
Local irradiation significantly increases surgical complications and impairs quality of life.
Combination chemotherapy alone seems promising and provides similar benefit to chemoradiation as neoadjuvant therapy.
Early administration of systemic therapy is also proved beneficial for long-term survival.
The purpose of this study is to compare the efficacy of chemotherapy alone with short-term modified FOLFOXIRI or long-term mFOLFOX with standard chemoradiation as neoadjuvant therapy for locally advanced rectal cancer.
Detailed description
Patients with cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT scan will be randomized to the following three groups:
Group A: Traditional chemoradiation.
Fluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY.
At the end of chemoradiation, patients will receive an evaluation with MR and CT scan.
If the efficacy is defined as CR, PR or SD, the TME will be performed in 6-8 weeks since the last irradiation.
If the disease progress with the possibility of R0 resection, the operation will be given soon.
If the tumor progress to impossible for R0 resection, the salvage chemotherapy will be given accordingly.
Adjuvant chemotherapy of 6-8 cycles of mFOLFOX will be administered 3-4 weeks after R0 resection.
Group B: Short-term mFOLFOXIRI.
Oxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended.
Patients are planned to receive 4 cycles of mFOLFOXIRI regimen preoperatively and postoperatively, respectively.
Before operation, efficacy evaluations will be performed every two cycles by CT and MR scan.
If the evaluation is defined as no progression without severe toxicity, the next 2 cycles will be given.
If the primary lesion progress without distant metastasis, patients will be assigned to group A.
If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.
Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.
Group C: Long-term mFOLFOX.
Oxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days.
Patients are planned to receive 8-9 cycles of mFOLFOX regimen preoperatively and 3-4 cycles postoperatively.
Efficacy evaluations will be performed every three cycles by CT and MR scan before TME.
If the evaluation is defined as no progression without severe toxicity, the next 3 cycles of mFOLFOX will be given with the maximum of 9 cyces.
If the primary lesion progress without distant metastasis, patients will be assigned to group A.
If distant metastasis occurr during chemotherapy, patients will withdraw from the trial and be treated further at the discretion of attending physicians.
Postoperative chemotherapy will initiate 3-4 weeks after R0 resection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 5-Fu + RT | Active comparator | Radiation: Chemoradiation5Fu + RT for five weeks --- 6-8 weeks of interval --- TME --- mFOLFOX * 6-8 |
| mFOLFOXIRI | Experimental | Drug: FOLFOXIRI ProtocolmFOLFOXIRI * 4 --- TME --- mFOLFOXIRI * 4 |
| mFOLFOX | Experimental | Drug: Folfox ProtocolmFOLFOX * 9 --- TME --- mFOLFOX * 3 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 1）Age: 18 to 75 years old;
- 2）Histological diagnosis of rectal adenocarcinoma;
- 3）Distance form anal margin ≤ 12cm: cT3-4 or cN+ and cM0 by pelvic MR and chest + abdominal CT, estimated possible for R0 resection;
- 4）There is no signs of intestinal obstruction, or obstruction of intestinal after treating with proximal colostomy has been relieved;
- 5）Patients did not previously receive rectal surgery, chemotherapy or radiation therapy , biological treatment , except for endocrine therapy;
Key exclusion criteria (14 listed)
- 1）Arrhythmia requires treatment with antiarrhythmia (except for beta-blockers or digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the last 6 months) or congestive heart failure exceeding NYHA class II;
- 2）Severe hypertension with poor control;
- 3）History of HIV infection or active phase of chronic hepatitis B or C infection with high copy viral DNA;
- 4）Other active serious infections according to NCI-CTC version 4.0;
- 5）There is preoperative evidence for distant metastasis outside pelvis;
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 |
|---|---|---|
| ChemoradiationFluorouracil 225 mg/m2/day continuous intravenous infusion on weekdays for five weeks; local irradiation 2GY/day on weekdays, totally 50GY. | Radiation | 5-Fu + RT |
| FOLFOXIRI ProtocolOxaliplatin 85 mg/m2 on day 1; irinotecan 150 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days; prophylactic G-CSF support is recommended. | Drug | mFOLFOXIRI |
| Folfox ProtocolOxaliplatin 85 mg/m2 on day 1; leucovorin 400 mg/m2 on day 1; fluorouracil 400 mg/m2 bolus and 2400 mg/m2 civ over 46h; treatment will be repeated every 14 days. | Drug | mFOLFOX |
Primary outcome
Disease-free survival
Time frame: 3 years
The interval from randomization to local recurrence, distant metastasis, death or the last follow-up.
4 secondary outcomes
Recurrence-free survival
Time frame: 3 years
Metastasis-free survival
Time frame: 3 years
Surgical complication
Time frame: 3 years
Treatment related quality of life
Time frame: up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
- Individual participant dataSharing planned: No
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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.
Ping Lan, MD principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chemoradiation, FOLFOXIRI Protocol and Folfox Protocol in people with Rectal Cancer and Chemotherapy Effect, run by Sixth Affiliated Hospital, Sun Yat-sen 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 8 inclusion and 14 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: opening soon, as of the sponsor's last update on 5 Jun 2019. 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.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ping Lan, MD (86-20-38285497, lanping@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jun 2019.