Rectal Cancer Patients
Conditions
Keywords
Adebrelimab, Neoadjuvant, Locally Advanced/Low-Lying Rectal Cancer
Brief summary
To observe and evaluate the efficacy and safety of neoadjuvant long-course concurrent chemoradiotherapy combined with Adebrelimab and Apatinib Mesylate in the treatment of locally advanced rectal cancer and low-lying rectal cancer with sphincter-preservation demand.
Detailed description
The pathological complete response (pCR) rate of standard neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) is only 10%-15%, and patients with low-lying rectal cancer face difficulties in sphincter preservation, with their quality of life severely compromised. Immune checkpoint inhibitors combined with chemoradiotherapy have demonstrated potential to improve pCR rates, with the NECTAR study reporting a pCR rate of 40% and the VOLTAGE-A study showing a pCR rate of 30% in MSS patients. Anti-angiogenic agents can reverse the immunosuppressive tumor microenvironment and exert synergistic antitumor effects when combined with chemoradiotherapy and immunotherapy. Based on the above background, this study is a single-center, single-arm phase II clinical trial designed to enroll 43 patients with locally advanced rectal cancer and low-lying rectal cancer with sphincter-preservation demand, to explore the efficacy and safety of neoadjuvant long-course concurrent chemoradiotherapy (45-50 Gy/25 fractions, concurrent capecitabine) combined with Adebrelimab (an anti-PD-L1 monoclonal antibody) and Apatinib Mesylate (an anti-angiogenic TKI). This study aims to provide rectal cancer patients with novel therapeutic strategies offering higher remission rates and greater opportunities for sphincter preservation.
Interventions
DRUGLong-course concurrent chemoradiotherapy combined with Adebrelimab and Apatinib
Long-course concurrent chemoradiotherapy regimen: 45-50 Gy administered in 25 fractions, with concurrent capecitabine 1650 mg/m²/day, bid on days 1-14, every 3 weeks as one cycle. Adebrelimab: 1200 mg, intravenous infusion, on D1, once every 3 weeks. Apatinib: 250 mg, orally, 5 days on and 2 days off; if the patient cannot tolerate the toxicity, the dose may be reduced to 125 mg once daily. Each cycle is 21 days, with a total of 6 cycles of neoadjuvant therapy before surgery. Efficacy evaluation is performed after every 2 cycles. After 6 cycles of long-course concurrent chemoradiotherapy combined with Adebrelimab and Apatinib, the research team will reassess the patient. For resectable patients, surgery will be performed 4-6 weeks after neoadjuvant therapy. For patients who decline surgery or are deemed unfit for surgery after 6 cycles, if the investigator believes that continued treatment with Adebrelimab and Apatinib may still provide benefit, the treatment may be continued until
Sponsors
Harbin Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 to 75 years, male or female; 2. Histologically or cytologically confirmed rectal cancer with measurable tumor lesion(s) (spiral CT or MRI scan ≥10 mm, meeting RECIST 1.1 criteria); 3. Clinical stage: rectal cancer cT3-4N0M0 or cT1-4N+M0, and low rectal cancer with a sphincter-preservation requirement (distance from the anal verge \<5 cm; stage T2N0M0); 4. Expected survival \>3 months; 5. ECOG PS score: 0-1; 6. No peritoneal metastasis or other distant metastasis; 7. No prior radiotherapy or immune checkpoint inhibitor therapy for rectal cancer; 8. Adequate function of vital organs as required (without the use of any blood components or cell growth factors during screening): Absolute neutrophil count ≥1.5×10⁹/L; platelet count ≥80×10⁹/L; hemoglobin ≥8.5 g/dL; Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, T3 and T4 levels should also be assessed; patients with normal T3 and T4 levels may be enrolled); Bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN; Serum creatinine ≤1.5×ULN; 9. Women of childbearing potential must have a negative pregnancy test (β-HCG) before starting treatment. Women of childbearing potential and men (who are sexually active with women of childbearing potential) must agree to use effective contraception consistently during treatment and for 6 months after the last dose; 10. Subjects voluntarily participate in the study and sign the informed consent form.
Exclusion criteria
1. Prior pelvic or abdominal radiotherapy; 2. Tumor expected to be unresectable after neoadjuvant therapy; 3. Pregnant or breastfeeding women, or women/ men of childbearing potential who refuse to use contraceptive measures; 4. History of other malignancies within the past 5 years, except for adequately treated cervical carcinoma in situ or cutaneous squamous cell carcinoma, or well-controlled basal cell carcinoma of the skin; 5. Uncontrolled symptomatic brain metastases, or poorly controlled psychiatric disorders, or severe intellectual or cognitive impairment; 6. Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severely impaired pulmonary function; 7. Active, known, or suspected autoimmune disease. Subjects with stable conditions not requiring systemic immunosuppressive therapy are eligible, e.g., type 1 diabetes, hypothyroidism requiring hormone replacement therapy, and skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, and alopecia); 8. Congestive heart failure, uncontrolled arrhythmia, myocardial infarction within 6 months, unstable angina, stroke or transient ischemic attack, severe hypertension refractory to medication, or other conditions rendering the patient unable to tolerate surgery; 9. Severe active infection requiring intravenous antibiotic therapy during the screening period; 10. Known allergy to the study drug or any of its excipients, or a history of severe allergic reaction to other monoclonal antibodies; 11. Clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to enrollment; 12. Hypertension that remains uncontrolled despite antihypertensive therapy prior to enrollment; 13. Patients with dysphagia; 14. Receipt of or planned receipt of live vaccines within 30 days prior to administration of adebrelimab; 15. Known history of HIV infection, or active hepatitis B or hepatitis C; 16. Inability to comply with the study protocol or to cooperate with follow-up; 17. Other conditions that the investigator considers inappropriate for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (cCR+pCR) | cCR assessed after neoadjuvant therapy; pCR assessed within 2 weeks post-surgery; assessed up to 6 months. | Proportion of patients achieving clinical complete response (cCR, no tumor residue by imaging and endoscopy) after neoadjuvant therapy or pathological complete response (pCR, no residual viable tumor cells in the tumor bed, %RVT=0) post-surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Imaging assessment after every 2 cycles（21 days per cycle） of treatment and post-surgery; assessed up to 6 months. | Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1 criteria on imaging. |
| Pathological Complete Response (pCR) | Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; assessed up to 6 months. | Proportion of patients with no residual viable tumor cells in the tumor bed (%RVT=0) after neoadjuvant therapy and surgery |
| Tumor Regression Grade (TRG): | Assessed via pathological examination of surgical specimens within 2 weeks post-surgery; assessed up to 6 months. | Assessment of pathological tumor regression grade per CAP criteria (grades 0-3), where grade 0 indicates complete regression (no viable tumor cells microscopically) and grade 3 indicates poor or no regression. |
| Sphincter Preservation Rate | Assessed within 2 weeks post-surgery; assessed up to 6 months. | Proportion of patients with low-lying rectal cancer who successfully preserve the anal sphincter and undergo low/ultra-low anastomosis. |
| Disease-Free Survival (DFS) | Time from first treatment to recurrence or death (whichever occurs first), assessed up to 36 months. | Time from enrollment to disease recurrence or death due to disease progression. |
| Overall Survival (OS) | Time from first treatment to death from any cause, assessed up to 36 months. | Time from first study drug administration to death from any cause. |
| Adverse Event Rate | Continuous monitoring from informed consent to 90 days after the last dose; assessed up to 36 months. | Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and treatment-related adverse events (TRAEs) graded per NCI-CTCAE v6.0; surgical complications graded per Clavien-Dindo classification. |
| Quality of Life (EORTC QLQ-CR29) | Assessed at baseline, pre-surgery post-neoadjuvant therapy, and at 3, 6, and 12 months post-surgery (5 time points in total); assessed up to 12 months. | Assessment of bowel symptoms, sexual function, and overall quality of life; higher scores indicate worse symptoms or better function. |
| Anal Function (LARS Score) | Assessed at baseline, pre-surgery post-neoadjuvant therapy, and at 3, 6, and 12 months post-surgery (5 time points in total);assessed up to 12 months. | Assessment of low anterior resection syndrome, total score 0-42 (0-20: no/mild LARS; 21-29: moderate; 30-42: severe). |
| Biomarker Exploration | Baseline tumor tissue and peripheral blood collected. Peripheral blood sampled 3 times during treatment (pre-RT, post-RT, and pre-surgery); tissue collected once at baseline only. Assessed up to 6 months. | Collection of tumor tissue and peripheral blood samples for genomic, transcriptomic, proteomic, and immune microenvironment analyses to identify potential predictive and prognostic biomarkers associated with efficacy and safety of neoadjuvant immunotherapy. |
Countries
China
Outcome results
None listed