Trial Title:
Single-arm, Single-center, Exploratory Phase II Clinical Study of Envafolimab Combined With Chemoradiotherapy in the Treatment of Locally Advanced pMMR/MSS Rectal Cancer
NCT ID:
NCT06239870
Condition:
Envafolimab Combined With Chemoradiotherapy in the Treatment of Locally Advanced pMMR/MSS Rectal Cancer
Conditions: Official terms:
Rectal Neoplasms
Conditions: Keywords:
Local progressive stage
Rectal cancer
Full neoadjuvant therapy
pMMR/MSS
Envafolimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Envafolimab combined with chemoradiotherapy in the whole course of neoadjuvant therapy
Description:
Each enrolled patient was given 2 cycles of induction chemotherapy combined with
immunization, followed by immunization combined with chemoradiotherapy, and finally 2
cycles of consolidation chemotherapy combined immunization
Arm group label:
neoadjuvant therapy
Summary:
Preoperative radiotherapy combined with 5-fluorouracil/capecitabine is currently the
standard treatment for locally advanced rectal cancer. Although this strategy effectively
reduces the risk of local recurrence, it fails to effectively improve the overall
survival rate of patients . The root cause is that 5-fluorouracil/capecitabine based
local radiotherapy is not effective in controlling potential micrometastases. Therefore,
many studies try to combine preoperative radiotherapy with more intense chemotherapy and
targeted drugs at the same time, as well as induction chemotherapy before preoperative
radiotherapy and consolidation chemotherapy after, in order to obtain better efficacy.
However, a number of studies have shown that increasing cytotoxic drugs fail to
effectively improve pathologic complete response rate (pCR) and long-term survival rate,
and significantly increase therapeutic toxicity . Therefore, the idea of trying to
increase the efficacy of cytotoxic drugs by accumulating them does not work.Based on the
use of PD-1/PD-L1 antibody in colorectal cancer and other solid tumors, and referring to
the scheme of PD-1/PD-L1 antibody combined with radiotherapy in other solid tumors, we
added envafolimab to local radiotherapy for advanced rectal cancer for exploration, with
a view to further improving the pCR rate and long-term survival of patients.
Detailed description:
Inclusion criteria：
1. Disease characteristics • Histologically confirmed rectal adenocarcinoma;
Immunohistochemical confirmation as pMMR or/and pCR or/and NGS test as MSS;
• Tumor location within 12cm from anal margin;
- Locally advanced rectal cancer (stage II-III, i.e. cT3-4 and/or N+) as assessed
by the UICC/AJCC TNM staging system (8th edition, 2017);
* Preoperative staging method: pelvic MRI/ transrectal ultrasound combined with
preoperative staging.
- No signs of intestinal obstruction; Or intestinal obstruction has been relieved
after proximal colostomy surgery;
- Preoperative chest, abdominal and pelvic CT to exclude distant metastasis.
2. Patient characteristics
• Age: 18 ~75 years old;
- Activity status score: ECOG 0-1;
- Life expectancy: more than 2 years;
- Hematology: WBC>3500×106/L; PLT>100000×106/L; Hb>10g/dL;
- Liver function: SGOT and SGPT are less than 1.5 times of normal value;
Bilirubin less than 1.5mg/dL;
- Kidney function: creatinine <1.8mg/dL;
- Other: non-pregnant or breastfeeding women; No other malignant disease (other
than non-melanoma or carcinoma in situ of the cervix) within 5 years or during
the same period; Does not have a mental illness that prevents informed consent;
There were no other serious diseases associated with shorter survival.
- Patients or family members can understand the study protocol and are willing to
participate in the study, and sign a written informed consent;
- Good patient compliance, voluntary follow-up, treatment, laboratory tests, and
other research steps as scheduled.
3. Prior treatment • No previous rectal cancer surgery;
• No previous chemotherapy or radiation therapy;
• No previous biotherapy;
• Previous endocrine therapy: No restriction.
Exclusion criteria：
• CRC for microsatellite highly unstable (MSI-H) or mismatch repair protein
expression deficiency (dMMR);
• Chronic hepatitis B or C with a history or active HIV infection (high copy of
viral DNA);
• Autoimmune diseases;
• Other active clinical serious infections (>NCI-CTC version 3.0);
• Stage I patients;
• Preoperative evidence of distant metastasis;
• Dysfluid, organ function decompensation;
• A history of pelvic or abdominal radiotherapy;
- Multiple primary cancers;
- Patients whose seizures require management (such as steroid or antiepileptic
therapy);
- A history of other malignancies within 5 years, except for cured cervical
carcinoma insitu or skin basal cell carcinoma;
- Chronic inflammatory bowel disease, intestinal obstruction; Substance abuse and
medical, psychological or social conditions that may interfere with the
patient's participation in the study or the evaluation of the findings;
- A known or suspected allergy to the study drug or to any drug administered in
connection with this trial;
- Any unstable conditions or conditions that could compromise patient safety and
compliance;
Describe the medication or treatment in detail:
1.1 Induction therapy stage (2 cycles of chemotherapy combined with immunotherapy)
1 Envafolimab: 200mg, subcutaneous injection, Q2W, 2 cycles (simultaneous administration
on the first day of chemotherapy).
2mFOLFOX6: Q2W, 2 cycles: oxaliplatin 85mg/m2 intravenous infusion for 2h, day 1. Calcium
folinate 400mg/m2 intravenous infusion for 2 hours, day 1. Fluorouracil was injected
intravenously at 400mg/m2 on day 1, followed by 1200mg/ (m2·d) × 2d with continuous
intravenous infusion (total 2400mg/m2, infusion for 46~48h). 1.2 Simultaneous
chemoradiotherapy (long-term radiotherapy
Chemotherapy combined with immunotherapy for 3 cycles)
Radiation therapy: 50Gy/25f, 2Gy daily, 5 days a week for 5 weeks.
Body position fixation: prone position, full bladder, body fixator or vacuum bag
fixation;
CT scan: Before the scan, intravenous contrast agent was injected to develop the
intestine, fill the bladder, empty the intestine, and collect two sets of CT images of
plain scan and enhanced phase (only plain scan images can be collected for those allergic
to contrast agent).
Radiotherapy equipment: linear accelerator;
Target area and irradiation field: The target area includes the primary rectal area and
lymphatic drainage area. The treatment plan is designed by IMRT radiotherapy. The target
area coverage and normal tissue limit are determined by the radiotherapy doctor according
to the specific conditions of the patient.
2 Capecitabine: 825mg/m2 orally (1650mg/m2/d) twice a day in the morning and evening, 5
days a week, synchronized with radiation therapy, for a total of 25 days.
3 Envafolimab: 200mg, subcutaneous injection, Q2W, 3 cycles (given on day 1, day 15, day
29 of radiotherapy).
1.3 Consolidation treatment stage (2 cycles of chemotherapy combined with immunotherapy)
1. Envafolimab: 200mg, subcutaneous injection, Q2W, 2 cycles, synchronous
administration on the first day of chemotherapy.
2. mFOLFOX6: Q2W, 2 cycles: oxaliplatin 85mg/m2 intravenous infusion for 2h, day 1.
Calcium folinate 400mg/m2 intravenous infusion for 2 hours, day 1. Fluorouracil was
injected intravenously at 400mg/m2 on day 1, followed by 1200mg/ (m2·d) ×2d with
continuous intravenous infusion (total 2400mg/m2, infusion for 46~48h).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1) Disease characteristics
- Histologically confirmed rectal adenocarcinoma; Immunohistochemical
confirmation as pMMR or/and pCR or/and NGS test as MSS;
- Tumor location within 12cm from anal margin;
- Locally advanced rectal cancer (stage II-III, i.e. cT3-4 and/or N+) as assessed
by the UICC/AJCC TNM staging system (8th edition, 2017);
* Preoperative staging method: pelvic MRI/ transrectal ultrasound combined with
preoperative staging.
- No signs of intestinal obstruction; Or intestinal obstruction has been relieved
after proximal colostomy surgery;
- Preoperative chest, abdominal and pelvic CT to exclude distant metastasis. 2)
Patient characteristics
- Age: 18 ~75 years old;
- Activity status score: ECOG 0-1;
- Life expectancy: more than 2 years;
- Hematology: WBC>3500×106/L; PLT>100000×106/L; Hb>10g/dL;
- Liver function: SGOT and SGPT are less than 1.5 times of normal value;
Bilirubin less than 1.5mg/dL;
- Kidney function: creatinine <1.8mg/dL;
- Other: non-pregnant or breastfeeding women; No other malignant disease (other
than non-melanoma or carcinoma in situ of the cervix) within 5 years or during
the same period; Does not have a mental illness that prevents informed consent;
There were no other serious diseases associated with shorter survival.
- Patients or family members can understand the study protocol and are willing to
participate in the study, and sign a written informed consent;
- Good patient compliance, voluntary follow-up, treatment, laboratory tests, and
other research steps as scheduled.
3) Prior treatment
- No previous rectal cancer surgery;
- No previous chemotherapy or radiation therapy;
- No previous biotherapy;
- Previous endocrine therapy: No restriction.
Exclusion Criteria:
- CRC for microsatellite highly unstable (MSI-H) or mismatch repair protein expression
deficiency (dMMR); Chronic hepatitis B or C with a history or active HIV infection
(high copy of viral DNA);
- Autoimmune diseases;
- Other active clinical serious infections (>NCI-CTC version 3.0);
- Stage I patients;
- Preoperative evidence of distant metastasis;
- Dysfluid, organ function decompensation;
- A history of pelvic or abdominal radiotherapy;
- Multiple primary cancers;
- Patients whose seizures require management (such as steroid or antiepileptic
therapy);
- A history of other malignancies within 5 years, except for cured cervical
carcinoma in situ or skin basal cell carcinoma;
- Chronic inflammatory bowel disease, intestinal obstruction; Substance abuse and
medical, psychological or social conditions that may interfere with the
patient's participation in the study or the evaluation of the findings;
- A known or suspected allergy to the study drug or to any drug administered in
connection with this trial;
- Any unstable conditions or conditions that may compromise patient safety and
compliance
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Envafolimab
Address:
City:
Kunming
Zip:
650000
Country:
China
Status:
Recruiting
Contact:
Last name:
Yunfeng Li, master
Phone:
13330445776
Email:
13330445776@qq.com
Contact backup:
Last name:
Xuan Zhang, doctoral candidate
Phone:
17387911546
Email:
1025415085@qq.com
Start date:
April 1, 2023
Completion date:
September 30, 2025
Lead sponsor:
Agency:
Yunnan Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
Beijing Bethune Charitable Foundation
Agency class:
Other
Source:
Yunnan Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06239870
