Rectal CancerPhase 2iMHRT-LARCNCT06599827
Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk LARC
A Phase 2 study testing moderately hypofractionated radiotherapy, chemotherapy and immunotherapy in people with Rectal Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
This study aims to evaluate the effectiveness and safety of combining moderately hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant treatment for high-risk locally advanced rectal cancer. 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?
- moderately hypofractionated radiotherapy, chemotherapy and immunotherapy
- 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
- 54 participants
- Where
- 1 siteChina
- Study dates
- 20 Sep 2024to 20 Sep 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 and ≤75 years.
- MRI-confirmed rectal adenocarcinoma with the lower edge of the lesion ≤10cm from the anal verge.
- Immunohistochemistry confirms proficiency in DNA mismatch repair (pMMR), or genetic testing confirms microsatellite instability-low (MSI-L) or microsatellite stable (MSS) status.
- Pelvic MRI showing one of the following high-risk factors: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph nodes.
- ECOG performance status of 0-1.
- No prior surgery, radiotherapy, chemotherapy, or targeted therapy.
- Tolerable to radiotherapy, chemotherapy, and immunotherapy with laboratory results: WBC ≥4.0 × 10^9/L, platelets ≥100 × 10^9/L, hemoglobin ≥80g/L, ALT \<2ULN, TB \<35μmol/L, Scr \<1.5ULN or creatinine clearance rate ≥50mL/min, TSH ≤ULN (if abnormal, consider T3 and T4 levels; if T3 and T4 are normal, patients can still be included).
- Voluntary participation with signed informed consent.
Who cannot join
- Distant metastases.
- Stage I or II rectal cancer not requiring neoadjuvant therapy.
- Severe cardiovascular, pulmonary, neurological, renal, gastrointestinal, or systemic diseases.
- Untreated chronic hepatitis B carrier with HBV DNA \>500 IU/ml, HCV RNA positive patients, except for inactive hepatitis B surface antigen carriers, stable hepatitis B (HBV DNA \<500 IU/ml), and cured hepatitis C patients.
- History of active autoimmune diseases or potential relapse of autoimmune diseases.
- Patients who received corticosteroids (equivalent to prednisone \>10mg/day) or other immunosuppressive therapy within 2 weeks prior to study drug administration.
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- History of thyroid dysfunction.
- Severe chronic or active infections requiring systemic antifungal or antiviral therapy, including tuberculosis.
- Known allergy or hypersensitivity to multiple drugs.
- History of pelvic radiation.
- History of inflammatory bowel disease.
- Unwillingness to participate or sign informed consent.
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
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200030
Genwen Chen, MD, PhD, +86-15802123840, chengenwen@fudan.edu.cn
About this study
Official title: Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk PMMR/MSS Locally Advanced Rectal Cancer: a Prospective, Exploratory Phase II Trial（iMHRT-LARC）
This study aims to evaluate the effectiveness and safety of combining moderately hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant treatment for high-risk locally advanced rectal cancer.
Read the detailed description
This study investigates a novel treatment approach involving moderately hypofractionated radiotherapy (3-3.5Gy×10) combined with chemotherapy and immunotherapy for patients with high-risk locally advanced rectal adenocarcinoma, aiming to optimize treatment efficacy and patient outcomes.
Neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer, improving surgical resection rates, local control, and sphincter preservation. Conventional long-course radiotherapy is the standard modality for neoadjuvant therapy, but it has drawbacks such as long treatment duration, high cost, and prolonged preoperative waiting time. Short-course radiotherapy, on the other hand, offers shorter treatment duration, lower cost, and shorter preoperative waiting time, but it is associated with higher rates of local recurrence. Immunotherapy has demonstrated promising anti-tumor activity in colorectal cancers with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) status, but its role in proficient mismatch repair (pMMR) and/or microsatellite stable (MSS) colorectal cancers remains unclear. However, studies have shown that the combination of chemoradiotherapy and immunotherapy can increase the pathologic complete response rate compared to chemoradiotherapy alone, suggesting that radiotherapy may serve as a stimulator of adaptive immunity and synergize with immunotherapy. Therefore, this study aims to explore the following regimen: neoadjuvant moderately hypofractionated radiotherapy at a dose of 3.5 Gy × 10 fractions to the tumors and 3 Gy × 10 fractions to the pelvic lymph node drainage area, combined with chemotherapy (capecitabine and oxaliplatin) and immunotherapy (Serplulimab).
This prospective, single-center, non-randomized Phase II trial is designed to explore the efficacy and safety of the treatment regimen. Patients will receive CapeOx chemotherapy, anti-PD-1 monoclonal antibody immunotherapy, and a course of moderately hypofractionated radiotherapy. The trial protocol prioritizes safety monitoring and efficacy assessments through standardized clinical and imaging evaluations.
- Conditions
- Rectal Cancer
- Being tested
- moderately hypofractionated radiotherapy, chemotherapy, immunotherapy, Total mesorectal excision (TME) surgery
- Keywords
- Moderately Hypofractionated Radiotherapy, Immunotherapy, Locally Advanced Rectal Adenocarcinoma, Chemotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
moderately hypofractionated radiotherapyRadiation
35 Gy in 10 fractions to mesorectal and metastatic lymph nodes, and 30 Gy in 10 fractions to pelvic lymphatic drainage area, weekly over 5 days at 3-3.5 Gy/day.
chemotherapyDrug
CapeOx-Capecitabine 1000 mg/m² orally twice daily (days 1-14, every 21 days) + Oxaliplatin 130 mg/m² IV (day 1, every 21 days).
immunotherapyDrug
Serplulimab 300 mg IV infusion on day 1 every 21 days.
Total mesorectal excision (TME) surgeryProcedure or surgery
Total mesorectal excision (TME) surgery assessment post 3 cycles of chemotherapy and immunotherapy; eligible patients undergo TME surgery.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Experimental | This study examines combined radiotherapy, chemotherapy, and immunotherapy for high-risk locally advanced rectal cancer. After a week post-radiotherapy, patients start CapeOx chemotherapy with anti-PD-1 mAb. Surgery follows after 3 cycles of this regimen. Receives: Radiation: moderately hypofractionated radiotherapy; Drug: chemotherapy; Drug: immunotherapy; Procedure: Total mesorectal excision (TME) surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathologic complete response (pCR)
Proportion of patients in whom no cancer cells are found in resected rectal tissue and regional lymph nodes upon pathological evaluation.
Measured: 30-day
Secondary outcomes (8)
disease-free survival (DFS)
DFS is defined as the time from randomization until disease recurrence or death from any cause.
Measured: 3-year
event-free survival (EFS)
Time from treatment initiation to occurrence of any of the following: disease progression affecting surgery, post-operative disease progression or recurrence, or death from any cause.
Measured: 3-year
objective response rate (ORR)
Proportion of patients showing partial or complete response to treatment, defined by RECIST v1.1 as ORR=(CR+PR)/ITT*100%.
Measured: 3-month
overall survival (OS)
OS is defined as the time from randomisation to death.
Measured: 3-year
adverse events
Incidence of adverse events: According to CTCAE 5.0.
Measured: 3-year
Quality of Life (QoL)-LARS socre
LARS score questionnaire: A tool used to assess bowel function and quality of life after rectal surgery, focusing on symptoms like frequency of bowel movements, urgency, and incontinence. The score ranges from 0 to 42, with higher scores indicating more severe symptoms and a greater impact on quality of life.
Measured: 3-year
Quality of Life (QoL)-Wexner score
Wexner score: Wexner score composed of five items (solid, liquid, gas, wears pad, and lifestyle alteration) and five frequencies, resulting in a total score ranging from 0 (perfect continence) to 20 (complete incontinence). The score includes pad usage and lifestyle alteration, providing a comprehensive assessment of the impact of fecal incontinence on a patient\'s daily life
Measured: 3-year
Quality of Life (QoL)-FISI score
FISI score: The Fecal Incontinence Severity Index, a questionnaire that quantifies the impact of fecal incontinence on quality of life by assessing the frequency of incontinence episodes and related concerns. It includes four types of incontinence (gas, mucus, liquid, solid) and six frequencies, plus a \"never\" option. Each item is scored according to its frequency, and the total score ranges from 0 to 61, with higher scores indicating greater severity and impact on the patient\'s life.
Measured: 3-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start20 Sep 2024 (estimated)
- Primary completion20 Sep 2026 (estimated)
- Study completion20 Sep 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 Shanghai Zhongshan 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
- Not applicable
- Intervention model
- Single group
- Model description
- Patients will receive CapeOx chemotherapy, anti-PD-1 mAb immunotherapy, and moderately hypofractionated radiotherapy.
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jian Wang, MD, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06599827
- Sponsor's protocol ID
- B2024-271
- Acronym
- iMHRT-LARC
- Status last verified
- Sep 2024
- First submitted
- 5 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk PMMR/MSS Locally Advanced Rectal Cancer: a Prospective, Exploratory Phase II Trial（iMHRT-LARC）
- ClinicalTrials.gov ID
- NCT06599827
- Acronym / sponsor ID
- iMHRT-LARC / B2024-271
- Conditions
- Rectal Cancer
- Keywords
- Moderately Hypofractionated Radiotherapy, Immunotherapy, Locally Advanced Rectal Adenocarcinoma, Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 20 Sep 2024 (estimated)
- Primary completion
- 20 Sep 2026 (estimated)
- Study completion
- 20 Sep 2029 (estimated)
- First posted
- 19 Sep 2024 (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 study aims to evaluate the effectiveness and safety of combining moderately hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant treatment for high-risk locally advanced rectal cancer.
Detailed description
This study investigates a novel treatment approach involving moderately hypofractionated radiotherapy (3-3.5Gy×10) combined with chemotherapy and immunotherapy for patients with high-risk locally advanced rectal adenocarcinoma, aiming to optimize treatment efficacy and patient outcomes.
Neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer, improving surgical resection rates, local control, and sphincter preservation. Conventional long-course radiotherapy is the standard modality for neoadjuvant therapy, but it has drawbacks such as long treatment duration, high cost, and prolonged preoperative waiting time. Short-course radiotherapy, on the other hand, offers shorter treatment duration, lower cost, and shorter preoperative waiting time, but it is associated with higher rates of local recurrence. Immunotherapy has demonstrated promising anti-tumor activity in colorectal cancers with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) status, but its role in proficient mismatch repair (pMMR) and/or microsatellite stable (MSS) colorectal cancers remains unclear. However, studies have shown that the combination of chemoradiotherapy and immunotherapy can increase the pathologic complete response rate compared to chemoradiotherapy alone, suggesting that radiotherapy may serve as a stimulator of adaptive immunity and synergize with immunotherapy. Therefore, this study aims to explore the following regimen: neoadjuvant moderately hypofractionated radiotherapy at a dose of 3.5 Gy × 10 fractions to the tumors and 3 Gy × 10 fractions to the pelvic lymph node drainage area, combined with chemotherapy (capecitabine and oxaliplatin) and immunotherapy (Serplulimab).
This prospective, single-center, non-randomized Phase II trial is designed to explore the efficacy and safety of the treatment regimen. Patients will receive CapeOx chemotherapy, anti-PD-1 monoclonal antibody immunotherapy, and a course of moderately hypofractionated radiotherapy. The trial protocol prioritizes safety monitoring and efficacy assessments through standardized clinical and imaging evaluations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will receive CapeOx chemotherapy, anti-PD-1 mAb immunotherapy, and moderately hypofractionated radiotherapy.
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Experimental | Radiation: moderately hypofractionated radiotherapy, Drug: chemotherapy, Drug: immunotherapy, Procedure: Total mesorectal excision (TME) surgeryThis study examines combined radiotherapy, chemotherapy, and immunotherapy for high-risk locally advanced rectal cancer. After a week post-radiotherapy, patients start CapeOx chemotherapy with anti-PD-1 mAb. Surgery follows after 3 cycles of this regimen. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥18 and ≤75 years.
- MRI-confirmed rectal adenocarcinoma with the lower edge of the lesion ≤10cm from the anal verge.
- Immunohistochemistry confirms proficiency in DNA mismatch repair (pMMR), or genetic testing confirms microsatellite instability-low (MSI-L) or microsatellite stable (MSS) status.
- Pelvic MRI showing one of the following high-risk factors: cT4a/b; N2; extramural vascular invasion (EMVI+); mesorectal fascia involvement (MRF+); enlarged lateral lymph nodes.
- ECOG performance status of 0-1.
Key exclusion criteria (12 listed)
- Distant metastases.
- Stage I or II rectal cancer not requiring neoadjuvant therapy.
- Severe cardiovascular, pulmonary, neurological, renal, gastrointestinal, or systemic diseases.
- Untreated chronic hepatitis B carrier with HBV DNA \>500 IU/ml, HCV RNA positive patients, except for inactive hepatitis B surface antigen carriers, stable hepatitis B (HBV DNA \<500 IU/ml), and cured hepatitis C patients.
- History of active autoimmune diseases or potential relapse of autoimmune diseases.
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 |
|---|---|---|
| moderately hypofractionated radiotherapy35 Gy in 10 fractions to mesorectal and metastatic lymph nodes, and 30 Gy in 10 fractions to pelvic lymphatic drainage area, weekly over 5 days at 3-3.5 Gy/day. | Radiation | Experimental group |
| chemotherapyCapeOx-Capecitabine 1000 mg/m² orally twice daily (days 1-14, every 21 days) + Oxaliplatin 130 mg/m² IV (day 1, every 21 days). | Drug | Experimental group |
| immunotherapySerplulimab 300 mg IV infusion on day 1 every 21 days. | Drug | Experimental group |
| Total mesorectal excision (TME) surgeryTotal mesorectal excision (TME) surgery assessment post 3 cycles of chemotherapy and immunotherapy; eligible patients undergo TME surgery. | Procedure or surgery | Experimental group |
Primary outcome
pathologic complete response (pCR)
Time frame: 30-day
Proportion of patients in whom no cancer cells are found in resected rectal tissue and regional lymph nodes upon pathological evaluation.
8 secondary outcomes
disease-free survival (DFS)
Time frame: 3-year
event-free survival (EFS)
Time frame: 3-year
objective response rate (ORR)
Time frame: 3-month
overall survival (OS)
Time frame: 3-year
adverse events
Time frame: 3-year
Quality of Life (QoL)-LARS socre
Time frame: 3-year
Quality of Life (QoL)-Wexner score
Time frame: 3-year
Quality of Life (QoL)-FISI score
Time frame: 3-year
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 19 Sep 2024.
- 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.
Jian Wang, MD principal investigator
Fudan University
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 moderately hypofractionated radiotherapy, chemotherapy and immunotherapy in people with Rectal Cancer, run by Shanghai Zhongshan 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 8 inclusion and 12 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 19 Sep 2024. 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 Genwen Chen, MD, PhD (86-021-64041990 ext. +86-1580212730, chengenwen@fudan.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathologic complete response (pCR) (time frame: 30-day). 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 19 Sep 2024.