Rectal NeoplasmsPhase 2RAICNCT05307198
Rectal Artery Infusion Chemotherapy Combined With Anti-PD1 Antibody for MSS LARC
A Phase 2 study testing Oxaliplatin, Rectectomy and Capecitabine in people with Rectal Neoplasms, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- Oxaliplatin, Rectectomy and Capecitabine
- 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
- 38 participants
- Where
- 1 siteChina
- Study dates
- 11 May 2022to 25 Apr 2025
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically diagnosed rectal adenocarcinoma
- Age ≥18 years old and ≤75 years old
- MRI stage T3-4aNany and TanyN1-2, but not T4b and no distant metastasis
- Life expectancy of 1 year The above
- Informed consent, no contraindications to chemotherapy exist
- The distance from the lower edge of the tumor to the anus is between 5cm to 12cm by MRI
Who cannot join
- Refused to participate in this study
- Multifocal colorectal cancer
- Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
- Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
- Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), ASA score> 3
- Mental disorder or illiteracy or language and communication barriers cannot understand the research plan
Show all 15Show fewer
- There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulant drugs and cannot be stopped, etc
- Rectal tumor has obstruction or high risk of obstruction and or there is bleeding and/or perforation
- Peripheral sensory nerve disorder, unable to receive oxaliplatin chemotherapy
- Lateral pelvic lymph node metastasis (mainly supplied by internal iliac artery)
- Pregnancy or breastfeeding
- Unable to accept MRI examination
- Consecutive use of glucocorticoids for more than 3 days within 1 month before signing the consent form
- Tumor directly invades or adheres to adjacent organs、structures(T4b) or tumor invaded MRF（Mesoretal Fascia）
- Other scenarios deemed inappropriate by the investigators
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Yurong Jiao, +8613732206364, jiaoyurong1990@163.com
About this study
Official title: Rectal Artery Infusion Chemotherapy of Oxaliplatin Plus Capecitabine Combined With Anti-PD1 Antibody After Induction Chemotherapy for Microsatellite Stable Locally Advanced Rectal Cancer：a Prospective Single-arm Phase II Study
The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer.
Read the detailed description
Neoadjuvant chemoradiation is the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy can achieve a pathological complete response rate (pCR) of about 20%. However, radiotherapy can cause tissue edema and fibrosis, increasing the risk of anastomotic leakage, resulting in rectal, urinary, and sexual dysfunction. Neoadjuvant chemotherapy or immunotherapy can avoid these adverse reactions, but the pCR rate of chemotherapy is significantly lower than that of neoadjuvant radiotherapy, and immunotherapy is less effective for MSS patients with weak immunogenicity. This study is a prospective, single-arm, single-center trial. The study will enhance the local killing effect of oxaliplatin through rectal artery infusion and induce immunogenic cell death (ICD) to enhance tumor antigen presentation, and then combine anti-PD1 antibody for neoadjuvant therapy. The study will address whether this treatment combination achieves pCR rates that are non-inferior to neoadjuvant RT for MSS-type locally advanced rectal cancer. It is known that the effective rate of oxaliplatin-containing intravenous chemotherapy for colorectal cancer is about 60%. In this study, 2 cycles of XELOX induction chemotherapy were firstly performed to screen out patients who were sensitive to chemotherapy. These patients were then infused with oxaliplatin via the superior rectal artery and oral capecitabine, combined with anti-PD1 antibody therapy for 2 cycles, and then underwent TME surgery. The primary endpoint of the study was the pCR rate.
- Conditions
- Rectal Neoplasms
- Being tested
- Oxaliplatin, Rectectomy, Capecitabine, Anti-PD-1 monoclonal antibody
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Drug: Oxaliplatin Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.
The dose of oxaliplatin used for rectal artery infusion was uncertain because there were no previous study. We design this study with Oxaliplatin 85mg/㎡for rectal artery infusion chemotherapy in Day 1 every 3 weeks and repeat for 2 cycles, based on intravenous chemotherapy regimens recommended by NCCN（mFolfox6）.If there were severe side effects caused by oxaliplatin observed within first 5 patients, we would decreasing the dose of oxaliplatin depending on the multidisciplinary discussion of researchers.
We acknowledged that our study did not determine the most appropriate dosage of oxaliplatin used for artery infusion, but rather performed a novel therapeutic method for microsatellite stable locally advanced rectal cancer.
RectectomyProcedure or surgery
Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).
CapecitabineDrug
Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 4 cycles.
Anti-PD-1 monoclonal antibodyDrug
Also called Sintilimab
Anti-PD1 antibody 200mg/m2 in Day 2 after Rectal Artery Infusion Chemotherapy. Repeat every 3 weeks for 2 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Rectal Artery Infusion Chemotherapy | Experimental | Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. Receives: Drug: Oxaliplatin; Procedure: Rectectomy; Drug: Capecitabine; Drug: Anti-PD-1 monoclonal antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate
the pathological complete remission rate of the rectal carcinoma
Measured: 1 day of postoperative pathological examination.
Secondary outcomes (7)
DFS
3-year Disease-free survival
Measured: From date of first chemotherapy until the date of first documented recurrence of tumor or date of death from any cause，whichever came first，assessed up to 36 months.
AE
the rate of adverse event（AE）
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving TME operation, up to 20 weeks
Surgical Complication
the rate of surgical complication during or after operation
Measured: within 30 days since operation
low anterior resection syndrome score
Low anterior resection syndrome (LARS) score of different time during treatment. The range (0-42) was divided into 0 to 20 (no LARS), 21 to 29 (minor LARS), and 30 to 42 (major LARS).
Measured: 3 months after operation; 6 months after operation;12 months after operation
Concentration of FLT3LG
Fms Related Receptor Tyrosine Kinase 3 Ligand is a marker of immunogenic cell death
Measured: blood test of FLT3LG at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Concentration of cytokines
blood density measurement of immunoreaction associated cytokines
Measured: blood test of cytokines at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Concentration of DAMP
blood density measurement of damage-associated molecular pattern（DAMP）
Measured: blood test of DAMP at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start11 May 2022
- Primary completion25 Apr 2024 (estimated)
- Study completion25 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- The pCR rate of neoadjuvant chemoradiotherapy is about 20% (null hypothesis). Assuming that the pCR of the RAIC scheme in this study would be in the range of 15%-35%. Using Simon's two-stage design, a total of 37 patients would provide 80% power at a one sided 5% alpha level. Considering the drop rate of 10%, 38 patients would be included (64 cases to be screened) in this study. 10 cases (17 cases were screened) and 28 cases (47 cases were screened) would be included in the first and second stages, respectively. If the number of patients with pCR in the first stage is less than 2, the study will be terminated. If the number of patients with pCR in the first stage is more than 2, a second-stage trial will be performed. If the total number of patients with pCR is more than 9, the effective remission rate of the RAIC regimen is considered to be acceptable.
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jun Li, MD, Study director, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05307198
- Sponsor's protocol ID
- Jun Li
- Acronym
- RAIC
- Status last verified
- Feb 2023
- First submitted
- 10 Jan 2022
- Last updated
- 10 Oct 2023
- 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 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rectal Artery Infusion Chemotherapy of Oxaliplatin Plus Capecitabine Combined With Anti-PD1 Antibody After Induction Chemotherapy for Microsatellite Stable Locally Advanced Rectal Cancer：a Prospective Single-arm Phase II Study
- ClinicalTrials.gov ID
- NCT05307198
- Acronym / sponsor ID
- RAIC / Jun Li
- Conditions
- Rectal Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 11 May 2022 (actual)
- Primary completion
- 25 Apr 2024 (estimated)
- Study completion
- 25 Apr 2025 (estimated)
- First posted
- 1 Apr 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.
The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer.
Detailed description
Neoadjuvant chemoradiation is the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy can achieve a pathological complete response rate (pCR) of about 20%. However, radiotherapy can cause tissue edema and fibrosis, increasing the risk of anastomotic leakage, resulting in rectal, urinary, and sexual dysfunction. Neoadjuvant chemotherapy or immunotherapy can avoid these adverse reactions, but the pCR rate of chemotherapy is significantly lower than that of neoadjuvant radiotherapy, and immunotherapy is less effective for MSS patients with weak immunogenicity. This study is a prospective, single-arm, single-center trial. The study will enhance the local killing effect of oxaliplatin through rectal artery infusion and induce immunogenic cell death (ICD) to enhance tumor antigen presentation, and then combine anti-PD1 antibody for neoadjuvant therapy. The study will address whether this treatment combination achieves pCR rates that are non-inferior to neoadjuvant RT for MSS-type locally advanced rectal cancer. It is known that the effective rate of oxaliplatin-containing intravenous chemotherapy for colorectal cancer is about 60%. In this study, 2 cycles of XELOX induction chemotherapy were firstly performed to screen out patients who were sensitive to chemotherapy. These patients were then infused with oxaliplatin via the superior rectal artery and oral capecitabine, combined with anti-PD1 antibody therapy for 2 cycles, and then underwent TME surgery. The primary endpoint of the study was the pCR rate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The pCR rate of neoadjuvant chemoradiotherapy is about 20% (null hypothesis). Assuming that the pCR of the RAIC scheme in this study would be in the range of 15%-35%. Using Simon's two-stage design, a total of 37 patients would provide 80% power at a one sided 5% alpha level. Considering the drop rate of 10%, 38 patients would be included (64 cases to be screened) in this study. 10 cases (17 cases were screened) and 28 cases (47 cases were screened) would be included in the first and second stages, respectively. If the number of patients with pCR in the first stage is less than 2, the study will be terminated. If the number of patients with pCR in the first stage is more than 2, a second-stage trial will be performed. If the total number of patients with pCR is more than 9, the effective remission rate of the RAIC regimen is considered to be acceptable.
| Arm | Type | Receives |
|---|---|---|
| Rectal Artery Infusion Chemotherapy | Experimental | Drug: Oxaliplatin, Procedure: Rectectomy, Drug: Capecitabine, Drug: Anti-PD-1 monoclonal antibodyPatients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pathologically diagnosed rectal adenocarcinoma
- Age ≥18 years old and ≤75 years old
- MRI stage T3-4aNany and TanyN1-2, but not T4b and no distant metastasis
- Life expectancy of 1 year The above
- Informed consent, no contraindications to chemotherapy exist
Key exclusion criteria (15 listed)
- Refused to participate in this study
- Multifocal colorectal cancer
- Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
- Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
- Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), ASA score> 3
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 |
|---|---|---|
| OxaliplatinDrug: Oxaliplatin Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles. The dose of oxaliplatin used for rectal artery infusion was uncertain because there were no previous study. We design this study with Oxaliplatin 85mg/㎡for rectal artery infusion chemotherapy in Day 1 every 3 weeks and repeat for 2 cycles, based on intravenous chemotherapy regimens recommended by NCCN（mFolfox6）.If there were severe side effects caused by oxaliplatin observed within first 5 patients, we would decreasing the dose of oxaliplatin depending on the multidisciplinary discussion of researchers. We acknowledged that our study did not determine the most appropriate dosage of oxaliplatin used for artery infusion, but rather performed a novel therapeutic method for microsatellite stable locally advanced rectal cancer. | Drug | Rectal Artery Infusion Chemotherapy |
| RectectomyInclude anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME). | Procedure or surgery | Rectal Artery Infusion Chemotherapy |
| CapecitabineOral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 4 cycles. | Drug | Rectal Artery Infusion Chemotherapy |
| Anti-PD-1 monoclonal antibodyAlso: SintilimabAnti-PD1 antibody 200mg/m2 in Day 2 after Rectal Artery Infusion Chemotherapy. Repeat every 3 weeks for 2 cycles. | Drug | Rectal Artery Infusion Chemotherapy |
Primary outcome
pCR rate
Time frame: 1 day of postoperative pathological examination.
the pathological complete remission rate of the rectal carcinoma
7 secondary outcomes
DFS
Time frame: From date of first chemotherapy until the date of first documented recurrence of tumor or date of death from any cause，whichever came first，assessed up to 36 months.
AE
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving TME operation, up to 20 weeks
Surgical Complication
Time frame: within 30 days since operation
low anterior resection syndrome score
Time frame: 3 months after operation; 6 months after operation;12 months after operation
Concentration of FLT3LG
Time frame: blood test of FLT3LG at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Concentration of cytokines
Time frame: blood test of cytokines at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Concentration of DAMP
Time frame: blood test of DAMP at baseline , pre-intervention of neoadjuvant chemotherapy, pre-intervention of artery infusion chemotherapy and pre-surgery.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Rectal Neoplasms
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. This study is not recruiting at the moment.
Jun Li, MD study director
Second Affiliated Hospital, Zhejiang University, School of Medicine
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 Oxaliplatin, Rectectomy and Capecitabine in people with Rectal Neoplasms, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 6 inclusion and 15 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 10 Oct 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li Jun, MD (+86 13777878061, 2307016@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate (time frame: 1 day of postoperative pathological examination.). 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 10 Oct 2023.