Locally Advanced Rectal CancerPhase 2TIMENT-RNCT05507112
TIME in Immunotherapy Combined With nCRT for Rectal Cancer
A Phase 2 study testing PD-1 inhibitor, Capecitabine and Long-course radiation therapy in people with Locally Advanced Rectal Cancer, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
This is an open-label, prospective phase II clinical trial to evaluate the therapeutic and prognostic implications of tumor immune microenvironment in the neoadjuvant immunotherapy combined with chemoradiotherapy for patients with rectal cancer. A total of 100 patients will be enrolled in this trial. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Rectal Cancer
- What is being tested?
- PD-1 inhibitor, Capecitabine and Long-course radiation therapy
- 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
- 100 participants
- Where
- 1 siteChina
- Study dates
- 20 Dec 2022to 1 Dec 2029
- 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
- Age ≥ 18 years and ≤75 years on the day of signing informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Histologically proven rectal adenocarcinoma.
- <12 cm from anal verge.
- Clinical stage of T3/T4 or N positive and M0
- No previous chemotherapy, radiotherapy, immunotherapy or surgical treatment
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- No immune system disease (e. g. systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis, scleroderma, mixed connective tissue disease, dermatomyositis (DM), hyperthyroidism, hypothyroidism, ulcerative colitis (UC), autoimmune hemolytic anemia (AIHA) or human immunodeficiency virus (HIV) infection.
- Adequate hepatic and renal function to chemoradiotherapy, immunotherapy and surgery.
- Willing and able to provide written informed consent.
Who cannot join
- Allergic to any component of chemotherapy or immunotherapy;
- Patients with multiple primary colorectal cancer;
- Other malignant tumors within 5 years, except for adequately treated cervical carcinoma in situ or cutaneous basal cell carcinoma, or basically controlled localized prostate cancer or surgically excised ductal carcinoma in situ of breast;
- Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgical resection;
- Prior or planed organ/bone marrow transplant
- Patients who receive systemic steroid therapy or immunosuppressive agents within 30 days before enrollment in the study;
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- Pregnant or lactating women
- Patients with a history of severe mental illness or being unable to comply with the research protocols.
- Patients who have contraindications to chemoradiotherapy, immunotherapy or surgery.
- Patients who have any other conditions that investigator judges unsuitable to participate.
Trial locations and contacts
1 site in 1 country.
China1 site
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
About this study
Official title: The Therapeutic and Prognostic Implications of Tumor Immune Microenvironment in The Neoadjuvant Immunotherapy Combined With Chemoradiotherapy for Rectal Cancer
This is an open-label, prospective phase II clinical trial to evaluate the therapeutic and prognostic implications of tumor immune microenvironment in the neoadjuvant immunotherapy combined with chemoradiotherapy for patients with rectal cancer. A total of 100 patients will be enrolled in this trial. The primary endpoint is the complete response rate, defined as the proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment. The long-term prognosis and adverse effects will also be evaluated and analyzed.
Read the detailed description
Objectives:
- To clarify the efficacy and safety of combined therapy for locally advanced rectal cancer (LARC) patients and verify the efficacy and safety of neoadjuvant immunotherapy for dMMR/MSI-H LARC patients.
- To clarify the effect of nCRT on TIME for rectal cancer, and the further effect of adding Immunotherapy.
- To verify the feasibility of predicting the efficacy of combined therapy by the infiltration level of CD8+ PD1+ TILs in tumor tissue before treatment in pMMR/MSS LARC patients and explore the comprehensive prediction index of the efficacy of combined therapy for LARC patients.
- To clarify the potential mechanism of immune response or immune escape to neoadjuvant immunotherapy for LARC patients.
- Conditions
- Locally Advanced Rectal Cancer
- Being tested
- PD-1 inhibitor, Capecitabine, Long-course radiation therapy
- Keywords
- Rectal Cancer, Immunotherapy, neoadjuvant therapy, Tumor Immune Microenvironment
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 inhibitorDrug
Also called Tislelizumab
Tislelizumab (3 cycles): 200mg i.v. q3w on day 1 of each cycle, and starting from the second week after the start of radiotherapy
CapecitabineDrug
Also called Xeloda
Capecitabine 1650mg/m2/d orally twice-daily, 5 days a week for a total of 5 weeks.
Long-course radiation therapyRadiation
45-50 Gy/day, 5 days a week for a total of 5 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant chemoradiotherapy plus PD-1 inhibitor | Experimental | Capecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks.
Tislelizumab is given on day 1 of week 2, 5 and 8 at 200 mg i.v. 8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME).
If the investigator and the subject opt for a "watch-and-wait" strategy after completing neoadjuvant therapy, a one-year follow-up will be conducted. If no additional surgery is performed due to disease-related reasons by the end of the follow-up period, this outcome is recognized as a clinical complete response (cCR). Receives: Drug: PD-1 inhibitor; Drug: Capecitabine; Radiation: Long-course radiation therapy |
| Neoadjuvant chemoradiotherapy | Active comparator | Capecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks.
8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME). Receives: Drug: Capecitabine; Radiation: Long-course radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate (CR rate)
Proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment.
Measured: 1-2 weeks after surgery or assessment after termination of neoadjuvant treatment
Secondary outcomes (18)
Pathological tumor regression grade (CAP)
All tumor tissues will be analyzed by experienced pathologists. Determination of tumor regression will adopt College of American Pathologists (CAP) tumor regression grade, which are as follows: CAP0: No viable cancer cells (complete response); CAP1:Single cells or rare small groups of cancer cells (near complete response); CAP2: Residual cancer with evident tumor regression, but more than single cells or rare small groups of cancer cells (partial response); and CAP3: Extensive residual cancer with no evident tumor regression (poor or no response).
Measured: 1-2 weeks after surgery
Rate of tumor down-staging
The proportion of patients experiencing tumor down-staging will be assessed by pathology.
Measured: 1-2 weeks after surgery
Lymphocytes infiltration changes after treatment
The categories, number and distribution of lymphocytes infiltrated in tumor and tumor stroma are measured by Multiplex immunofluorescence assay.
Measured: 2 weeks before treatment and 1-2 weeks after surgery
The expression of immune-related pathways
The expression of immune-related pathways is measured by RNAseq.
Measured: 2 weeks before treatment and 1-2 weeks after surgery
Rectal MRI defined tumor regression
Proportion of patients achieving rectal MRI-confirmed near or complete tumor regression.
Measured: Baseline and 1 week before surgery
Rectal MRI defined tumor down-staging
Proportion of patients achieving rectal MRI-confirmed down-staging.
Measured: Baseline and 1 week before surgery
Rectal MRI defined tumor volume change
The change of patients' tumor volume will be confirmed by rectal MRI.
Measured: Baseline and 1 week before surgery
Local recurrence (LR) rate
Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology
Measured: 3, 5 years
Disease free survival (DFS)
The three-year and five-year disease-free survival of patients.
Measured: 3, 5 years
Disease-related Treatment Failure (DrTF) rate
DrTF was defined as the time from the initiation of radiotherpay to the date of each of the following, whichever occurred first: disease progression during/after treatment, distant metastasis at any timepoint, or death from any cause.
Measured: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Overall survival (OS)
The three-year and five-year overall survival of patients.
Measured: 3, 5 years
Surgical complications
Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc, which will also be assessed according to "Clavien-Dindo Classification of surgical complications".
Measured: The surgical complications are assessed up to 5 years from the surgery
R0 resection rate
Rate of complete tumor removal with negative microscopically resection margin.
Measured: Within two weeks after surgery
Rate of sphincter-sparing surgery
Rate of sphincter-sparing surgery if surgery is performed.
Measured: Within two weeks after surgery
Rate of adverse event
Rate of adverse events will be assessed according to National Cancer Institution Common Terminology Criteria of Adverse Events (NCI-CTCAE) v.4.02. Adverse events of this trial will include immune-related adverse events, chemo- and radiotherapy related adverse events, and combined treatment-related adverse events.
Measured: From date of randomization until the date of death from any cause, assessed up to 5 years
Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) (v 3.0)
Score values from 1 (not at all) to 4 (very much) respectively from 1 (very poor) to 7 (excellent). Score outcome depends on score type.
Measured: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29)
Score values from 1 (not at all) to 4 (very much). Score outcome depends on score type.
Measured: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Patient reported outcome: Functional outcome according to Wexner score
Five score values from "never" to "1 per day or more often". The more often the worse outcome.
Measured: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2022
- Study start20 Dec 2022
- Primary completion30 May 2025
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jiaolin Zhou, Ph.D, Study chair, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05507112
- Sponsor's protocol ID
- PUMCH_TIMENT-R
- Acronym
- TIMENT-R
- Status last verified
- Jul 2026
- First submitted
- 17 Jul 2022
- Last updated
- 7 Jul 2026
- 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 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Therapeutic and Prognostic Implications of Tumor Immune Microenvironment in The Neoadjuvant Immunotherapy Combined With Chemoradiotherapy for Rectal Cancer
- ClinicalTrials.gov ID
- NCT05507112
- Acronym / sponsor ID
- TIMENT-R / PUMCH_TIMENT-R
- Conditions
- Locally Advanced Rectal Cancer
- Keywords
- Rectal Cancer, Immunotherapy, neoadjuvant therapy, Tumor Immune Microenvironment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 20 Dec 2022 (actual)
- Primary completion
- 30 May 2025 (actual)
- Study completion
- 1 Dec 2029 (estimated)
- First posted
- 18 Aug 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.
This is an open-label, prospective phase II clinical trial to evaluate the therapeutic and prognostic implications of tumor immune microenvironment in the neoadjuvant immunotherapy combined with chemoradiotherapy for patients with rectal cancer. A total of 100 patients will be enrolled in this trial. The primary endpoint is the complete response rate, defined as the proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment. The long-term prognosis and adverse effects will also be evaluated and analyzed.
Detailed description
Objectives:
- To clarify the efficacy and safety of combined therapy for locally advanced rectal cancer (LARC) patients and verify the efficacy and safety of neoadjuvant immunotherapy for dMMR/MSI-H LARC patients.
- To clarify the effect of nCRT on TIME for rectal cancer, and the further effect of adding Immunotherapy.
- To verify the feasibility of predicting the efficacy of combined therapy by the infiltration level of CD8+ PD1+ TILs in tumor tissue before treatment in pMMR/MSS LARC patients and explore the comprehensive prediction index of the efficacy of combined therapy for LARC patients.
- To clarify the potential mechanism of immune response or immune escape to neoadjuvant immunotherapy for LARC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant chemoradiotherapy plus PD-1 inhibitor | Experimental | Drug: PD-1 inhibitor, Drug: Capecitabine, Radiation: Long-course radiation therapyCapecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks. Tislelizumab is given on day 1 of week 2, 5 and 8 at 200 mg i.v. 8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME). If the investigator and the subject opt for a "watch-and-wait" strategy after completing neoadjuvant therapy, a one-year follow-up will be conducted. If no additional surgery is performed due to disease-related reasons by the end of the follow-up period, this outcome is recognized as a clinical complete response (cCR). |
| Neoadjuvant chemoradiotherapy | Active comparator | Drug: Capecitabine, Radiation: Long-course radiation therapyCapecitabine 1650mg/m2 is given 5 days a week in parallel with radiotherapy 45 to 50 Gy during 5 consecutive weeks. 8-12 weeks after completion of radiation therapy, patients undergo total mesorectal excision (TME). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years and ≤75 years on the day of signing informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Histologically proven rectal adenocarcinoma.
- <12 cm from anal verge.
- Clinical stage of T3/T4 or N positive and M0
Key exclusion criteria (10 listed)
- Allergic to any component of chemotherapy or immunotherapy;
- Patients with multiple primary colorectal cancer;
- Other malignant tumors within 5 years, except for adequately treated cervical carcinoma in situ or cutaneous basal cell carcinoma, or basically controlled localized prostate cancer or surgically excised ductal carcinoma in situ of breast;
- Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, or other conditions requiring emergency surgical resection;
- Prior or planed organ/bone marrow transplant
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 |
|---|---|---|
| PD-1 inhibitorAlso: TislelizumabTislelizumab (3 cycles): 200mg i.v. q3w on day 1 of each cycle, and starting from the second week after the start of radiotherapy | Drug | Neoadjuvant chemoradiotherapy plus PD-1 inhibitor |
| CapecitabineAlso: XelodaCapecitabine 1650mg/m2/d orally twice-daily, 5 days a week for a total of 5 weeks. | Drug | Neoadjuvant chemoradiotherapy, Neoadjuvant chemoradiotherapy plus PD-1 inhibitor |
| Long-course radiation therapy45-50 Gy/day, 5 days a week for a total of 5 weeks. | Radiation | Neoadjuvant chemoradiotherapy, Neoadjuvant chemoradiotherapy plus PD-1 inhibitor |
Primary outcome
Complete response rate (CR rate)
Time frame: 1-2 weeks after surgery or assessment after termination of neoadjuvant treatment
Proportion of patients who achieve pathological complete response (pCR) or clinical complete response (cCR) without evidence of distant metastasis on post-treatment or preoperative assessment.
18 secondary outcomes
Pathological tumor regression grade (CAP)
Time frame: 1-2 weeks after surgery
Rate of tumor down-staging
Time frame: 1-2 weeks after surgery
Lymphocytes infiltration changes after treatment
Time frame: 2 weeks before treatment and 1-2 weeks after surgery
The expression of immune-related pathways
Time frame: 2 weeks before treatment and 1-2 weeks after surgery
Rectal MRI defined tumor regression
Time frame: Baseline and 1 week before surgery
Rectal MRI defined tumor down-staging
Time frame: Baseline and 1 week before surgery
Rectal MRI defined tumor volume change
Time frame: Baseline and 1 week before surgery
Local recurrence (LR) rate
Time frame: 3, 5 years
Disease free survival (DFS)
Time frame: 3, 5 years
Disease-related Treatment Failure (DrTF) rate
Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Overall survival (OS)
Time frame: 3, 5 years
Surgical complications
Time frame: The surgical complications are assessed up to 5 years from the surgery
R0 resection rate
Time frame: Within two weeks after surgery
Rate of sphincter-sparing surgery
Time frame: Within two weeks after surgery
Rate of adverse event
Time frame: From date of randomization until the date of death from any cause, assessed up to 5 years
Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) (v 3.0)
Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Patient reported outcome: Quality of life according to questionnaire European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29)
Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
Patient reported outcome: Functional outcome according to Wexner score
Time frame: Baseline and months 3, 6, 12, 18, 24, 36, 48, 60
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 7 Jul 2026.
- 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. This study is not recruiting at the moment.
Jiaolin Zhou, Ph.D study chair
Peking Union Medical College 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 PD-1 inhibitor, Capecitabine and Long-course radiation therapy in people with Locally Advanced Rectal Cancer, run by Peking Union Medical College Hospital 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: under way, not looking for participants, as of the sponsor's last update on 7 Jul 2026. 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?
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?
Complete response rate (CR rate) (time frame: 1-2 weeks after surgery or assessment after termination of neoadjuvant treatment). 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 7 Jul 2026.