Clinical trial NCT06919510: A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Ivonescimab and Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Official title: A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Lvonescimab and Chemotherapy Versus Neoadjuvant Short-course Radiotherapy Followed by Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Rectal Adenocarcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Akeso
First posted: 2025-04-09
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of short-course radiotherapy followed by ivonescimab and chemotherapy in participants with pMMR/MSS locally advanced rectal cancer. Patients were randomly assigned to experimental group A or control group B according to a 1:1 ratio. In group A, patients will receive neoadjuvant short-course radiotherapy followed by ivonescimab and chemotherapy. In group B, patients will receive neoadjuvant short-course radiotherapy followed by chemotherapy. After neoadjuvant treatment, the patients and investigator could choose one of the following treatments:(1) Surgery. The patients will receive surgery within 4-8 weeks after the last dose of capecitabine, and the surgical method is selected by the investigator, (2) Watch and Wait (only for patients with clinical complete response after neoadjuvant therapy).


Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 years;
2. ECOG perfommance status of 0 or 1;
3. Life expectancy: more than 2 years;
4. Histologically proven rectal adenocarcinoma;
5. Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;
6. According to the 8th Edition of the AJCC Staging Manual, clinical stage cT3-4NanyM0 or cTxN+M0 of II-III rectal cancer was determined by Magnetic resonance imaging (MRI)±transrectal ultrasonography/ ultrasound endoscopy. Lower edge of the tumor was ≤ 12 cm from the anal verge;
7. Eligible for R0 surgery;
8. No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;
9. Adequate organ function;
10. Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion Criteria:

1. Any distant metastasis or inoperable disease, regardless clinical stage;
2. Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;
3. Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;
4. Multiple primary rectal cancers;
5. Previous pelvic or abdominal radiotherapy;
6. Difficulty swallowing;
7. Current presence of uncontrolled combined disease;
8. Active clinical infections;
9. History of severe bleeding tendency or coagulation dysfunction;
10. Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;
11. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;
12. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;
13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival;

Primary outcomes:
measure: Adverse events
timeFrame: Through study completion, an average of 6 month
measure: Complete response rate
timeFrame: 4 weeks after curative surgery for pCR; 2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine) for cCR
measure: Clinical complete response rate
timeFrame: 2-4 weeks after the completion of neoadjuvant therapy (last dose of capecitabine)
Secondary outcomes:
measure: Pathologic complete response
timeFrame: 4 weeks after surgery
measure: TRG
timeFrame: 4 weeks after surgery
measure: R0 resection rate
timeFrame: 4 weeks after surgery
measure: Local recurrence
timeFrame: 3 years after Randomization
measure: Distant metastasis
timeFrame: 3 years after Randomization
measure: OS
timeFrame: 3 years after Randomization
measure: EFS
timeFrame: 3 years after Randomization
Other outcomes:
Locations:
Study officials:
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