Colorectal CancerPhase 2NCT05371197
Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer
A Phase 2 study testing Neoadjuvant therapy with PD-L1 inhibitor in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial summary
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% of all CRC patients, and can not benefit from 5-fluorouracil (5-FU) adjuvant… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)
- What is being tested?
- Neoadjuvant therapy with PD-L1 inhibitor
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteChina
- Study dates
- 5 May 2022to 31 Dec 2024
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]).
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- Non complicated primary tumor (obstruction, perforation, bleeding).
- No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy.
- Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.
Who cannot join
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
- Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
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- Breast- feeding or pregnant women
- Lack of effective contraception.
- Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
- With any distant metastasis.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
the Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong, 510630
Jiafeng Fang, M.D. & Ph.D., +8613760660785, fangjf@mail.sysu.edu.cn
Jiafeng Fang, M.D. & Ph.D.
About this study
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% of all CRC patients, and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in "N Engl J Med" showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response.
In theory, anti-PD-L1 drugs should have fewer immune side-effects than anti-PD-1 drugs. However, there are no reports of anti-PD-L1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to investigate the efficacy and safety of anti-PD-L1 monoclonal antibody (Envafolimab) as neoadjuvant immuntherapy for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.
- Conditions
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
- Being tested
- Neoadjuvant therapy with PD-L1 inhibitor
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant therapy with PD-L1 inhibitorDrug
Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab), 300mg, Q3W for 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| PD-L1 inhibitor | Experimental | Neoadjuvant therapy with PD-L1 inhibitor (Envafolimab) Receives: Drug: Neoadjuvant therapy with PD-L1 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rates
Proportion of patients experiencing a pCR to perioperative PD-L1 antibody
Measured: 1 year
Secondary outcomes (6)
Major pathological response rates
The proportion of patients experiencing a major pathological response to perioperative PD-L1 antibody
Measured: 1 year
R0 resection rates
The proportion of patients experiencing a R0 resection after perioperative treatment with PD-L1 antibody
Measured: 1 year
Disease-free survival (DFS)
Defined as the time from randomization to relapse, metastasis or death from any cause
Measured: 3 years
Overall survival (OS)
Defined as the time from randomization to death from any cause
Measured: 5 years
Drug Safety
Assessed by evaluation of treatment-related adverse events
Measured: 1 year
Drug feasibility
Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative toripalimab dose
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2022
- Study start5 May 2022
- Primary completion30 Jun 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal 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
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hongbo Wei, Third Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05371197
- Sponsor's protocol ID
- ENCC
- Status last verified
- May 2022
- First submitted
- 29 Nov 2021
- Last updated
- 12 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Envafolimab as Neoadjuvant Immuntherapy in Resectable Local Advanced dMMR/MSI-H Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05371197
- Acronym / sponsor ID
- ENCC
- Conditions
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Study start
- 5 May 2022 (actual)
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 12 May 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.
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% of all CRC patients, and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in "N Engl J Med" showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response.
In theory, anti-PD-L1 drugs should have fewer immune side-effects than anti-PD-1 drugs. However, there are no reports of anti-PD-L1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to investigate the efficacy and safety of anti-PD-L1 monoclonal antibody (Envafolimab) as neoadjuvant immuntherapy for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD-L1 inhibitor | Experimental | Drug: Neoadjuvant therapy with PD-L1 inhibitorNeoadjuvant therapy with PD-L1 inhibitor (Envafolimab) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (10 listed)
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
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 therapy with PD-L1 inhibitorNeoadjuvant therapy with PD-L1 inhibitor (Envafolimab), 300mg, Q3W for 4 cycles | Drug | PD-L1 inhibitor |
Primary outcome
Pathological complete response (pCR) rates
Time frame: 1 year
Proportion of patients experiencing a pCR to perioperative PD-L1 antibody
6 secondary outcomes
Major pathological response rates
Time frame: 1 year
R0 resection rates
Time frame: 1 year
Disease-free survival (DFS)
Time frame: 3 years
Overall survival (OS)
Time frame: 5 years
Drug Safety
Time frame: 1 year
Drug feasibility
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2022.
- Individual participant dataSharing planned: Undecided
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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.
the Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, China
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 Neoadjuvant therapy with PD-L1 inhibitor in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by Third Affiliated Hospital, 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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 12 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 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?
Results are not available in the source record.
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?
Pathological complete response (pCR) rates (time frame: 1 year). 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 12 May 2022.