Clinical trial NCT06760520: Short-course Radiotherapy Followed by CAPOX and Ivonescimab for Locally Advanced Rectal Cancer
Official title: A Single-arm, Prospective, Phase II Clinical Study of Short-course Radiotherapy Followed by CAPOX and Ivonescimab for Locally Advanced Low-middle Rectal Cancer with a High Risk of Recurrence
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Rectal Cancer
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2025-01-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-arm, prospective, phase II clinical study to evaluate the efficacy and safety of preoperative short-course radiotherapy combined with ivonescimab and chemotherapy + total mesorectal excision(TME) surgery in patients with advanced rectal cancer.

Detailed description: Studies included a screening period (no more than 28 days after participants signed informed consent form to 28 days before first dose), treatment (receiving appropriate treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death or study end, whichever occurs first), and follow-up (including safety follow-up and survival follow-up).

Eligible subjects will receive short-course radiotherapy (SCRT), pelvic 25Gy/5f/1 week. 1-2 weeks after the end of treatment, subjects continued to receive neoadjuvant chemotherapy combined with immunotherapy regimen for 4 cycles: ivonescimab 20 mg/kg, intravenous infusion every 3 weeks (Q3W), plus CAPOX (capecitabine: 850-1000mg/m2, bid, po, d1-14, oxaliplatin: 130mg/m2, ivgtt, d1), Q3W. Neoadjuvant therapy was assessed 2 weeks after the end of neoadjuvant therapy, and TME surgery was performed 4 weeks after the end of neoadjuvant therapy (R0 surgery was performed). Patients can choose to enter the organ preservation observation; If the efficacy after preoperative chemoradiotherapy is evaluated as clinical complete remission (cCR) and the patient strongly refuses surgery, the patient should be informed of the risk of recurrence and ask the patient to sign a rejection of surgery. Medication safety is assessed and, depending on the severity of adverse events (AEs) and drug relevance, investigators will take steps to ensure subject safety. After surgery (or patients who strongly refuse surgery) there is a 30- and 90-day safety follow-up, and survival assessments are performed every 3 months to obtain survival information and collect new tumor treatment information until the death of the participant, withdrawal of informed consent, or the end of the study, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* ECOG score of 0-1;
* histologically or cytologically confirmed colorectal adenocarcinoma with non-distant metastasis
* Tumor distance from anal verge ≦10cm
* at least one high-risk criterion defined by pelvic MRI: cT stage \>T2 (tumor invades intrinsic muscularis propria by more than 5 mm); Extramural vascular invasion; cN2; Involvement of the rectal mesorectal fascia (tumor or lymph node ≤1mm from the rectal mesorectal fascia); Lateral lymph node short diameter ≥5mm
* enough organ function

Exclusion Criteria:

* with known MSI-H or dMMR
* Multiple primary adenocarcinomas
* History of pelvic radiotherapy
* Previous immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibody, etc.), immunocellular therapy, and other treatments targeting the immune mechanism of the tumor.

Primary outcomes:
measure: Complete response rate (CR, pCR plus cCR )
timeFrame: pCR rate : within 1 week after surgery；cCR：12-13 weeks after radiotherapy ends
Secondary outcomes:
measure: 3-years DFS rate
timeFrame: From date of treatment until the date of first documented disease relapse or date of death from any cause, whichever came first about 3years.
measure: 5-years OS rate
timeFrame: From date of treatment until date of death from any cause,about 5 years
measure: ORR
timeFrame: up to 2 years
measure: Incidence and severity of adverse events (AEs)
timeFrame: up to 2 years
measure: Tumor downstaging rate
timeFrame: up to 2 years
measure: 2-year organ preservation observation rate
timeFrame: up to two years
measure: surgical complication
timeFrame: 30 days after surgery
Other outcomes:
Locations:
Study officials:
References: