Rectal CancerPhase 2TRACE-LENCT05969847
Organ Preservation Following Enverolimab-based Total Neoadjuvant Therapy for Locally Advanced Very Low Rectal Cancer
A Phase 2 study testing split-course hypofraction radiotherapy, CAPOX and Envafolimab in people with Rectal Cancer, run by 池畔 at 1 site in China.
Trial summary
Patients diagnosed with locally advanced very low rectal cancer were chosen to participate in a comprehensive neoadjuvant therapy (TNT) protocol. This treatment regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- split-course hypofraction radiotherapy, CAPOX and Envafolimab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteChina
- Study dates
- 15 Aug 2023to 31 Dec 2027
- Phase
- Phase 2
- 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
- Aged 18-75.
- Histopathology confirmed the rectal adenocarcinoma,cT3-4N0 or cT1-4N1-2. The tumor's lower margin ≤ 2cm from the anorectal ring's upper edge (based on MRI measurement).
- Eastern tumor cooperation group (ECOG) status:0-2.
- American Association of Anesthesiologists (ASA) status: I-III.
- No previous systemic therapy, including chemotherapy, immunotherapy, or radiotherapy for rectal cancer.
- No previous history of pelvic radiotherapy.
Show all 11Show fewer
- Sufficient organ function based on the following parameters:
- An absolute neutrophil count≥ 1.5 × 109 / L, a thrombocyte count ≥ 100 × 109/ L, a glomerular filtration rate (calculated using the Cockcroft-Gault formula) with a creatinine level ≤ 1.5 × ULN or a creatinine clearance > 50ml/min, and AST and ALT levels ≤ 2.5 × ULN or a total bilirubin level ≤ 1.5 × ULN.
- Effective contraception during the study.
- Patients are willing and able to comply with the protocol during the study period.
- Patients with written informed consent
Who cannot join
- Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, and adenocarcinoma developed from inflammatory bowel disease.
- Metastasis to para-aortic, lateral, or inguinal lymph nodes has been identified.
- Suspected distant metastasis in organs other than para-aortic, lateral, or inguinal lymph nodes is being considered.
- Known hypersensitivity to platinum drugs or capecitabine.
- Patients receiving concomitant treatment with drugs that interact with capecitabine or oxaliplatin (such as flucytosine, phenytoin, and warfarin).
- According to the New York Heart Association (NYHA) classification, III or IV heart failure, and angina pectoris have occurred in the past six months.
Show all 11Show fewer
- Uncontrolled active infection or severe concomitant systemic disease.
- Patients who need immunosuppressive therapy for organ transplantation.
- Uncontrolled epilepsy or mental illness.
- Pregnant or lactating female patients.
- Non-compliance or researchers believe that the patient will not be able to complete the entire trial
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
Pan Chi
Fuzhou, Fujian, 350001
Pan Chi, MD, +8613675089677, cp3169@163.com
Jiabin Zheng, +8613365910080, xhyykjk@163.com
About this study
Official title: Total Neoadjuvant Therapy With Split-course Hypofraction Radiotherapy Combined With CAPOX and Envafolimab Followed by Local Excision for Locally Advanced Very Low Rectal Cancer: an Open-label, Single-arm, Multi-center, Phase II Trial
Patients diagnosed with locally advanced very low rectal cancer were chosen to participate in a comprehensive neoadjuvant therapy (TNT) protocol. This treatment regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after undergoing TNT, an organ-preserving strategy involving local full-thickness resection was implemented.
Read the detailed description
Locally advanced very low rectal cancer poses significant challenges in rectal cancer treatment. Presently, the prevailing approach in clinical practice involves neoadjuvant chemoradiotherapy in conjunction with total mesorectal excision (TME). Historically, abdominoperineal resection (APR) has been the conventional surgical procedure for managing locally advanced very low rectal cancer. However, the long-term presence of a colostomy following an abdominoperineal resection (APR) significantly impacts the quality of life for patients. Additionally, studies have revealed that 11.8-22% of rectal cancer patients who underwent APR after neoadjuvant chemoradiotherapy (nCRT) achieved a pathological complete response (pCR). Conversely, 11-52% of patients with pCR after nCRT for rectal cancer ultimately underwent APR surgery. Intersphincter resection (ISR) offers a highly beneficial surgical approach that preserves the anal sphincter, particularly for individuals with locally advanced very low rectal cancer. The patient's postoperative quality of life was significantly affected by severe low anterior resection syndrome (LARS), sexual dysfunction, and voiding dysfunction.
This study represents an exploratory phase II clinical trial in which patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab.
For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after undergoing TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.
This study aims to investigate the effectiveness and safety of organ preservation using the local resection approach in patients with locally advanced very low rectal cancer. By implementing this approach, the study aims to improve the quality of life for patients who achieve pathological complete response (pCR), thereby avoiding the need for conventional abdominoperineal resection (APR) and intersphincteric resection (ISR) procedures. Additionally, this study aims to address the issue of local regrowth associated with the "watch \& wait" strategy and propose a novel treatment strategy for rectal-sparing surgery in patients with locally advanced very low rectal cancer.
- Conditions
- Rectal Cancer
- Being tested
- split-course hypofraction radiotherapy, CAPOX, Envafolimab, Local excision
- Keywords
- Locally advanced very low rectal cancer, Total neoadjuvant therapy, Hypofraction radiotherapy, CAPOX, Envafolimab, Local excision
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
split-course hypofraction radiotherapyRadiation
Also called hypofraction radiotherapy
After reaching a cumulative radiotherapy dose of 25Gy in the entire pelvic cavity (PTV1), the treatment field was subsequently narrowed to solely focus on the primary tumor (PTV2), with a total dose of 35Gy administered. All patients will undergo fractionated radiotherapy, following a regimen of 7Gy per fraction, delivered every 3 weeks for five cycles.
CAPOXDrug
Also called Capecitabine+Oxaliplatin
Drug: Oxaliplatin,130mg/m2，ivgtt，d1,for 6 cycles. Drug: Capecitabine,1000mg/m2，po，bid，d1-14, for 6 cycles.
EnvafolimabDrug
Also called KN035
Envafolimab is administered by subcutaneous injection. The recommended dose is 300 mg per 3 weeks (Q3W) for 6 cycles.
Local excisionProcedure or surgery
Local full-thickness resection is employed for patients with clinical complete response (cCR) or near-clinical complete response (ncCR) following TNT.
| Study group | Role | What they receive |
|---|---|---|
| split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision | Experimental | Patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab.
For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery. Receives: Radiation: split-course hypofraction radiotherapy; Drug: CAPOX; Drug: Envafolimab; Procedure: Local excision |
What is being measured
The primary outcome is the main question the study is designed to answer.
Organ preservation
The rectum is intact, owing to no radical total mesorectal excision (TME), curative (R0) salvage surgery by local excision (LE), and no permanent stoma (including a never reversed protective stoma or a stoma owing to toxicities and/or poor functional outcomes).
Measured: 36 months
Secondary outcomes (8)
ypT0-1 rate
The proportion of subjects with primary rectal cancer assessed by hematoxylin and eosin staining including no evidence of primary tumor (T0) or carcinoma in situ: intramucosal carcinoma (invading lamina propria, not infiltrating muscularis mucosa) (Tis) or tumor invading submucosa (T1) (ypT0-1 based on the latest UICC/AJCC staging system)
Measured: 36 months
Pathological complete response (pCR) rate
Proportion of subjects with primary rectal cancer and all sampled lymph nodes who did not find any invasive carcinoma and high-grade intraepithelial neoplasia/severe dysplasia after assessment by hematoxylin and eosin staining (Judged as ypT0N0 stage according to the latest UICC/AJCC staging system)
Measured: 36 months
Acute and late toxicity
Acute and late toxicity, Incidence of Treatment-Emergent Adverse Events assessment according to NCICTCAE V.5.0
Measured: 36 months
Local recurrence rate
The proportion of patients in all subjects within 3 years from the start of the surgery to detection of a tumor involving the bowel wall only that occurs after LE or TME
Measured: 36months
Local regional recurrence rate
The proportion of patients in all subjects within 3 years from the start of the surgery to detection of a tumor involving either the bowel wall, mesorectum, and/or pelvic organs that occurs after LE or TME
Measured: 36 months
Disease-free survival
The proportion of patients in all subjects within 3 years from the start of the surgery to recurrence, distant metastsis, or death from any cause (whichever occurs first)
Measured: 36 months
Quality of life-based on EORTC QLQ-C30 and EORTC QLQ-CR29
Quality of life measured using EORTC QLQ-C30 and EORTC QLQ-CR29
Measured: baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME
Anorectal function
Anorectal function based on LARS score
Measured: baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start15 Aug 2023 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 池畔
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, 池畔, Fujian Medical University Union Hospital
- Investigators
- Pan Chi, MD, Principal investigator, Fujian Medical University Union Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05969847
- Sponsor's protocol ID
- 2023XHYG0026-01
- Acronym
- TRACE-LE
- Status last verified
- Jul 2023
- First submitted
- 23 Jul 2023
- Last updated
- 1 Aug 2023
- 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 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Neoadjuvant Therapy With Split-course Hypofraction Radiotherapy Combined With CAPOX and Envafolimab Followed by Local Excision for Locally Advanced Very Low Rectal Cancer: an Open-label, Single-arm, Multi-center, Phase II Trial
- ClinicalTrials.gov ID
- NCT05969847
- Acronym / sponsor ID
- TRACE-LE / 2023XHYG0026-01
- Conditions
- Rectal Cancer
- Keywords
- Locally advanced very low rectal cancer, Total neoadjuvant therapy, Hypofraction radiotherapy, CAPOX, Envafolimab, Local excision
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- 池畔University, hospital or other
- Study start
- 15 Aug 2023 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 1 Aug 2023 (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.
Patients diagnosed with locally advanced very low rectal cancer were chosen to participate in a comprehensive neoadjuvant therapy (TNT) protocol. This treatment regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after undergoing TNT, an organ-preserving strategy involving local full-thickness resection was implemented.
Detailed description
Locally advanced very low rectal cancer poses significant challenges in rectal cancer treatment. Presently, the prevailing approach in clinical practice involves neoadjuvant chemoradiotherapy in conjunction with total mesorectal excision (TME). Historically, abdominoperineal resection (APR) has been the conventional surgical procedure for managing locally advanced very low rectal cancer. However, the long-term presence of a colostomy following an abdominoperineal resection (APR) significantly impacts the quality of life for patients. Additionally, studies have revealed that 11.8-22% of rectal cancer patients who underwent APR after neoadjuvant chemoradiotherapy (nCRT) achieved a pathological complete response (pCR). Conversely, 11-52% of patients with pCR after nCRT for rectal cancer ultimately underwent APR surgery. Intersphincter resection (ISR) offers a highly beneficial surgical approach that preserves the anal sphincter, particularly for individuals with locally advanced very low rectal cancer. The patient's postoperative quality of life was significantly affected by severe low anterior resection syndrome (LARS), sexual dysfunction, and voiding dysfunction.
This study represents an exploratory phase II clinical trial in which patients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab.
For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after undergoing TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery.
This study aims to investigate the effectiveness and safety of organ preservation using the local resection approach in patients with locally advanced very low rectal cancer. By implementing this approach, the study aims to improve the quality of life for patients who achieve pathological complete response (pCR), thereby avoiding the need for conventional abdominoperineal resection (APR) and intersphincteric resection (ISR) procedures. Additionally, this study aims to address the issue of local regrowth associated with the "watch \& wait" strategy and propose a novel treatment strategy for rectal-sparing surgery in patients with locally advanced very low rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision | Experimental | Radiation: split-course hypofraction radiotherapy, Drug: CAPOX, Drug: Envafolimab, Procedure: Local excisionPatients diagnosed with locally advanced very low rectal cancer were chosen to undergo a total neoadjuvant therapy (TNT) regimen. This regimen consisted of preoperative fractionated radiotherapy (5×7Gy) combined with 6 cycles of CAPOX chemotherapy and enverolimab. For patients who achieved clinical complete response (cCR) or near-clinical complete response (ncCR) after TNT, an organ-preserving strategy involving local full-thickness resection was implemented. Patients who achieve non-clinical complete response are subjected to traditional TME surgery. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Aged 18-75.
- Histopathology confirmed the rectal adenocarcinoma,cT3-4N0 or cT1-4N1-2. The tumor's lower margin ≤ 2cm from the anorectal ring's upper edge (based on MRI measurement).
- Eastern tumor cooperation group (ECOG) status:0-2.
- American Association of Anesthesiologists (ASA) status: I-III.
- No previous systemic therapy, including chemotherapy, immunotherapy, or radiotherapy for rectal cancer.
Key exclusion criteria (11 listed)
- Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, and adenocarcinoma developed from inflammatory bowel disease.
- Metastasis to para-aortic, lateral, or inguinal lymph nodes has been identified.
- Suspected distant metastasis in organs other than para-aortic, lateral, or inguinal lymph nodes is being considered.
- Known hypersensitivity to platinum drugs or capecitabine.
- Patients receiving concomitant treatment with drugs that interact with capecitabine or oxaliplatin (such as flucytosine, phenytoin, and warfarin).
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 |
|---|---|---|
| split-course hypofraction radiotherapyAlso: hypofraction radiotherapyAfter reaching a cumulative radiotherapy dose of 25Gy in the entire pelvic cavity (PTV1), the treatment field was subsequently narrowed to solely focus on the primary tumor (PTV2), with a total dose of 35Gy administered. All patients will undergo fractionated radiotherapy, following a regimen of 7Gy per fraction, delivered every 3 weeks for five cycles. | Radiation | split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision |
| CAPOXAlso: Capecitabine+OxaliplatinDrug: Oxaliplatin,130mg/m2，ivgtt，d1,for 6 cycles. Drug: Capecitabine,1000mg/m2，po，bid，d1-14, for 6 cycles. | Drug | split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision |
| EnvafolimabAlso: KN035Envafolimab is administered by subcutaneous injection. The recommended dose is 300 mg per 3 weeks (Q3W) for 6 cycles. | Drug | split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision |
| Local excisionLocal full-thickness resection is employed for patients with clinical complete response (cCR) or near-clinical complete response (ncCR) following TNT. | Procedure or surgery | split-course hypofraction radiotherapy plus CAPOX and Envafolimab followed by local excision |
Primary outcome
Organ preservation
Time frame: 36 months
The rectum is intact, owing to no radical total mesorectal excision (TME), curative (R0) salvage surgery by local excision (LE), and no permanent stoma (including a never reversed protective stoma or a stoma owing to toxicities and/or poor functional outcomes).
8 secondary outcomes
ypT0-1 rate
Time frame: 36 months
Pathological complete response (pCR) rate
Time frame: 36 months
Acute and late toxicity
Time frame: 36 months
Local recurrence rate
Time frame: 36months
Local regional recurrence rate
Time frame: 36 months
Disease-free survival
Time frame: 36 months
Quality of life-based on EORTC QLQ-C30 and EORTC QLQ-CR29
Time frame: baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME
Anorectal function
Time frame: baseline, 3 months, 12 months, 24 months, and 36 months after LE or TME
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 1 Aug 2023.
- Individual participant dataSharing planned: No
Related trials for Rectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Pan Chi, MD principal investigator
Fujian Medical University Union Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing split-course hypofraction radiotherapy, CAPOX and Envafolimab in people with Rectal Cancer, run by 池畔 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 11 inclusion and 11 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 1 Aug 2023. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Pan Chi, MD (+8613675089677, cp3169@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Organ preservation (time frame: 36 months). 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 1 Aug 2023.