Colon Cancer Stage IIPhase 3NCT05194878
Neoadjuvant FOLFOXIRI Versus Immediate Surgery for Stage II and III Colon Cancers
A Phase 3 study testing neoadjuvant chemotherapyI, Colectomy and adjuvant chemotherapy in people with Colon Cancer Stage II and Colon Cancer Stage III, run by Sun Yat-sen University at 1 site in China.
Trial summary
BACKGROUND: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colon Cancer Stage II, Colon Cancer Stage III
- What is being tested?
- neoadjuvant chemotherapyI, Colectomy and adjuvant chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2021to Dec 2026
- 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
- Histologically proven adenocarcinoma or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer of the colon(≥ 12 cm from the anal verge).
- pMMR in immunohistochemical detection or MSI-H in MSI test.
- Determined preoperatively by either spiral or multidetector CT: high risk T3 (tumor disruption of muscle wall and extension into pericolic fat with more than 5 mm protrusion into adjacent mesenteric fat) or T4 (tumor penetrates to the surface of the visceral peritoneum or directly invades or is adherent to adjacent organs or structures).
- Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
- Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
- Adequate renal biochemistry: serum creatinine was less than 1.5 times the normal value.
- Adequate hepatobiliary function: serum total bilirubin and ALT were less than 1.5 times the normal value.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Who cannot join
- Any patient for whom radiotherapy is advised by the MDT
- Strong evidence of distant metastases or peritoneal nodules (M1)
- dMMR in immunohistochemical detection or MSI-L/MS-S in MSI test.
- Peritonitis (secondary to perforated tumour)
- Colonic obstruction that has not been defunctioned
- Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
- Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
651 Dongfeng Road East
Guangzhou, Guangdong, 510060
Peirong Ding, Doctor, 13543478645 ext. +86, dingpr@sysucc.org.cn
Yuan Li, Doctor, 18816800377 ext. +86, liyuan@sysucc.org.cn
About this study
Official title: Phase III Study of Neoadjuvant FOLFOXIRI Chemotherapy Versus Immediate Surgery for High-risk Resectable Stage II and III Colon Cancers
BACKGROUND:
In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer.
Read more
OBJECTIVE:
The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.
Read the detailed description
This trial is a a two-arm, multicenter, open labelled, prospective, randomized phase III studies. Eligible patients with High-risk Resectable Stage II and III (T4 or T3 with extramural depth≧5 mm) colon cancer patients will be randomly assigned, in a 2:1 ratio, to receive either perioperative or postoperative chemotherapy.
- Conditions
- Colon Cancer Stage II, Colon Cancer Stage III
- Being tested
- neoadjuvant chemotherapyI, Colectomy, adjuvant chemotherapy
- Keywords
- neoadjuvent chemotherapy, FOLFOXIRI, colon caner
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
neoadjuvant chemotherapyIDrug
Also called mFOLFOXIR
mFOLFOXIRI (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV Irinotecan 150 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 48h every 14 days) for 6 cycles followed by colectomy (3 to 6 weeks after) . If PD was observed after 3 cycles, direct colectomy was performed.
ColectomyProcedure or surgery
Radical colectomy
adjuvant chemotherapyDrug
Also called FOLFOX/CapeOX/Cape
mFOLFOX6 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-Fluorouracil 400 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 46h every 14 days) . CAPOX (IV oxaliplatin given over 120 min at a dose of 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days) . Oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days. The plan and cycles are determined according to the surgical pathology and physical conditions.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant chemotherapy | Experimental | 12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy Receives: Drug: neoadjuvant chemotherapyI; Procedure: Colectomy |
| Postoperative chemotherapy | Active comparator | surgery followed by 24 weeks of FOLFOX or CapeOX or Cape Receives: Procedure: Colectomy; Drug: adjuvant chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Defined as the time from randomization to relapse or death, whichever occurred first
Measured: 2 years
Secondary outcomes (7)
Overall survival
Defined as the time from randomization to death from any cause
Measured: 5 years
Down-staging of primary tumors
Down-staging of the resected tumour as measured by histopathological tumour diameter and stage according to the TNM staging system of AJCC (7th version)
Measured: 1 year
Chemotherapy toxicity
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0
Measured: through chemotherapy administration, up to 6 months
R0 resection rate
Quality of resection specimen
Measured: after surgery completed, up to 1 month
Surgical morbidity
Complication after surgery
Measured: 30 days post surgery
CT staging
the accuracy of CT staging
Measured: from randomization to surgery completed, up to 6 months
CT assessment of response to neoadjuvant treatment
CT evaluation of the thickness of tumor walls or tumor diameter or tumor length. Efficacy evaluation will be assessed using the RECIST criteria, version 1.1.
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2022
- Study start1 Dec 2021
- Primary completionDec 2024 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon Cancer Stage IIStudies of the same condition, open and under way.
- More trials run by 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
- 840 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pei-Rong Ding, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05194878
- Sponsor's protocol ID
- 2021-FXY-244
- Status last verified
- Jan 2022
- First submitted
- 21 Dec 2021
- Last updated
- 18 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Study of Neoadjuvant FOLFOXIRI Chemotherapy Versus Immediate Surgery for High-risk Resectable Stage II and III Colon Cancers
- ClinicalTrials.gov ID
- NCT05194878
- Acronym / sponsor ID
- 2021-FXY-244
- Conditions
- Colon Cancer Stage II, Colon Cancer Stage III
- Keywords
- neoadjuvent chemotherapy, FOLFOXIRI, colon caner
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 840 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 18 Jan 2022 (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.
BACKGROUND:
In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography allows a good prediction of tumor stage (wall penetration and nodal involvement) prior to surgery. The investigators conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOXIRI regimen compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, High-risk, but resectable Stage II or III colon cancer.
OBJECTIVE:
The primary objective of this study is to evaluate the efficacy of perioperative chemotherapy with FOLFOXIRI regimen compared to postoperative chemotherapy in patients with High-risk Resectable Stage II and III colon cancer. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications.
Detailed description
This trial is a a two-arm, multicenter, open labelled, prospective, randomized phase III studies. Eligible patients with High-risk Resectable Stage II and III (T4 or T3 with extramural depth≧5 mm) colon cancer patients will be randomly assigned, in a 2:1 ratio, to receive either perioperative or postoperative chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant chemotherapy | Experimental | Drug: neoadjuvant chemotherapyI, Procedure: Colectomy12 weeks of FOLFOXIRI neuoadjuvantly followed by surgery and adjuvant chemotherapy |
| Postoperative chemotherapy | Active comparator | Procedure: Colectomy, Drug: adjuvant chemotherapysurgery followed by 24 weeks of FOLFOX or CapeOX or Cape |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically proven adenocarcinoma or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer of the colon(≥ 12 cm from the anal verge).
- pMMR in immunohistochemical detection or MSI-H in MSI test.
- Determined preoperatively by either spiral or multidetector CT: high risk T3 (tumor disruption of muscle wall and extension into pericolic fat with more than 5 mm protrusion into adjacent mesenteric fat) or T4 (tumor penetrates to the surface of the visceral peritoneum or directly invades or is adherent to adjacent organs or structures).
- Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
- Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
Key exclusion criteria (8 listed)
- Any patient for whom radiotherapy is advised by the MDT
- Strong evidence of distant metastases or peritoneal nodules (M1)
- dMMR in immunohistochemical detection or MSI-L/MS-S in MSI test.
- Peritonitis (secondary to perforated tumour)
- Colonic obstruction that has not been defunctioned
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 |
|---|---|---|
| neoadjuvant chemotherapyIAlso: mFOLFOXIRmFOLFOXIRI (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV Irinotecan 150 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 48h every 14 days) for 6 cycles followed by colectomy (3 to 6 weeks after) . If PD was observed after 3 cycles, direct colectomy was performed. | Drug | Neoadjuvant chemotherapy |
| ColectomyRadical colectomy | Procedure or surgery | Neoadjuvant chemotherapy, Postoperative chemotherapy |
| adjuvant chemotherapyAlso: FOLFOX/CapeOX/CapemFOLFOX6 (IV oxaliplatin given over 120 min at a dose of 85 mg/m2 on day 1 followed by IV leucovorin 400 mg/m2 over 2h, IV bolus 5-Fluorouracil 400 mg/m2 and IV infusional 5-Fluorouracil 2400 mg/m2 over 46h every 14 days) . CAPOX (IV oxaliplatin given over 120 min at a dose of 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days) . Oral capecitabine 1000 mg/m2 twice daily on days 1 through 14 every 21 days. The plan and cycles are determined according to the surgical pathology and physical conditions. | Drug | Postoperative chemotherapy |
Primary outcome
Disease-free survival
Time frame: 2 years
Defined as the time from randomization to relapse or death, whichever occurred first
7 secondary outcomes
Overall survival
Time frame: 5 years
Down-staging of primary tumors
Time frame: 1 year
Chemotherapy toxicity
Time frame: through chemotherapy administration, up to 6 months
R0 resection rate
Time frame: after surgery completed, up to 1 month
Surgical morbidity
Time frame: 30 days post surgery
CT staging
Time frame: from randomization to surgery completed, up to 6 months
CT assessment of response to neoadjuvant treatment
Time frame: up to 6 months
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 18 Jan 2022.
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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.
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 neoadjuvant chemotherapyI, Colectomy and adjuvant chemotherapy in people with Colon Cancer Stage II and Colon Cancer Stage III, run by Sun Yat-sen University at 1 site 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 8 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 18 Jan 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 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?
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival (time frame: 2 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 18 Jan 2022.