Planned organ preservation after neoadjuvant chemotherapy for low rectal cancer

Planed Organ Preservation for Early- and Intermediate-risk Low Rectal Cancer With Good Response to Neoadjuvant Chemotherapy

This trial tests whether adding immunotherapy to long-course chemoradiotherapy and consolidation chemotherapy helps more people with low to intermediate-risk low rectal cancer keep their rectum after an initial good response to XELOX chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 186 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: tislelizumab, chemotherapy, prednisone, immunotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07070622 on ClinicalTrials.gov

What this trial studies

Adults with low or intermediate-risk low rectal adenocarcinoma who show a radiologic response (≥30% shortening of tumor long diameter on MRI) after two cycles of XELOX are randomized to standard total neoadjuvant therapy (long-course chemoradiotherapy plus consolidation chemotherapy) or the same regimen with added immunotherapy. The main goal is to compare organ preservation rates between the two groups following effective initial chemotherapy. Eligibility requires pMMR/MSS status, tumors ≤5 cm in diameter within 5 cm of the anal verge, cT1-3abN0-1M0 disease, and ECOG 0-1. All participants are treated and followed at West China Hospital with imaging and clinical assessments per protocol.

Who should consider this trial

Good fit: Ideal candidates are adults 18–80 years old with untreated, pMMR/MSS low or intermediate-risk low rectal adenocarcinoma (cT1-3abN0-1M0), tumor ≤5 cm and within 5 cm of the anal verge, ECOG 0–1, who show ≥30% tumor shrinkage on MRI after two cycles of XELOX.

Not a fit: Patients with high-risk or advanced features (MRF involvement, large or circumferential tumors, positive lateral nodes, cT4 or metastatic disease), those who do not respond to initial chemotherapy, or those with significant comorbidities are unlikely to benefit from the organ-preservation approach tested here.

Why it matters

Potential benefit: If successful, the approach could increase the proportion of patients who avoid radical rectal surgery and preserve anal function.

How similar studies have performed: Prior total neoadjuvant therapy studies have improved downstaging and organ preservation rates, but adding immunotherapy for pMMR/MSS low rectal cancer is a relatively novel approach with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

1. Age: 18-80 years old; Gender is not limited;
2. rectal adenocarcinoma confirmed by pathology and pMMR/MSS by immunohistochemistry and/or genetic testing;
3. The following characteristics of the tumor were evaluated by thoracoabdominal CT, rectal ultrasound and MRI: ① The distance between the lower edge of the tumor and the anal verge was ≤5cm measured by digital rectal examination or MRI; ② Clinical stage cT1-3abN0-1M0 (if cT1N0, patients suitable for endoscopic resection should be excluded); ③MRF (-) (\> 1mm), EMVI (±); ④ Lateral lymph nodes were negative and less than 7mm; ⑤ tumor diameter ≤5cm; ⑥ tumor circumference ≤2/3.
4. ECOG score: 0-1;
5. Patients with primary rectal cancer did not receive surgery, radiotherapy, chemotherapy or other anti-tumor treatment before enrollment;
6. Normal main organ function, which met the following characteristics: ① Blood routine examination criteria: HB ≥9g/dL, WBC ≥ 3.5/4.0×109/L, neutrophil ≥ 1.5×109/L, PLT≥ 100×109/L; ② Biochemical examination should meet the following criteria: Crea and BIL ≤ 1.0 times the upper limit of normal value (ULN), ALT and AST≤ 2.5 times the upper limit of normal value (ULN), alkaline phosphatase (ALP) ≤2.5×UNL, total bilirubin (Tbil) ≤1.5×UNL.
7. No history of allergy to 5-Fu or platinum drugs; Women of childbearing age were required to have a negative pregnancy test (serum or urine) 7 days before enrollment and to be willing to use an appropriate method of contraception during the trial and for 8 weeks after the last dose. For men, surgical sterilization or consent to use an appropriate method of contraception for the duration of the trial or for 8 weeks after the last dose;

(9) The subjects voluntarily joined the study, signed the informed consent form, with good compliance, and cooperated with follow-up.

Exclusion Criteria:

1. patients with lynch syndrome;
2. Distant metastasis was not considered at initial diagnosis but proved during treatment;
3. previous or concurrent history of other malignant tumors (including synchronous colon cancer), except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
4. patients who had received pelvic radiotherapy;
5. pregnant or lactating women with fertility needs; Male patients with fertility needs;
6. The presence of uncontrolled systemic diseases as determined by the investigator, including diabetes mellitus, hypertension, active autoimmune diseases or a history of autoimmune diseases (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism), and severe heart, lung, and kidney diseases; Subjects had active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL) and hepatitis C (hepatitis C antibody positive and HCV-RNA higher than the detection limit of the analytical method).
7. those with mental disorders;
8. Severe infection (CTCAE \> 2) occurred within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; Patients with active pulmonary inflammation on baseline chest imaging or signs and symptoms of infection requiring treatment with oral or intravenous antibiotics within 2 weeks before the first dose of study drug were excluded if prophylactic antibiotics were used.
9. patients with bleeding diathesis or coagulopathy were on thrombolytic/anticoagulant therapy; Aneurysm, stroke, transient ischemic attack, arteriovenous malformation in the past year;
10. serious gastrointestinal diseases affecting the absorption of oral chemotherapy drugs, and a history of gastrointestinal fistula, perforation, bleeding or severe ulcer;
11. a history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
12. patients with a history of interstitial lung disease, noninfectious pneumonia, pulmonary fibrosis or other uncontrolled acute lung disease, active pulmonary tuberculosis infection detected by medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment, or a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
13. known allergic to macromolecular protein preparations, or to any component of tislelizumab, or allergic, hypersensitive, or contraindicated to etoposide or cisplatin or any component used in their preparations;
14. have received or are receiving any of the following therapies: a. Anti-pd-1 or anti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy; b. received any study drug within 4 weeks before the first dose of the study drug; c. subjects requiring systemic treatment with corticosteroids (\> 10 mg prednisone equivalent daily) or other immunosuppressive agents within 2 weeks before the first dose of study drug, except when corticosteroids are used for local inflammation and to prevent allergy, nausea, and vomiting. Other special circumstances require communication with the sponsor. In the absence of active autoimmune disease, inhaled or topical steroids and adrenocortical hormone replacement at a therapeutic dose of prednisone of more than 10mg per day were allowed. d. vaccination with an antitumor vaccine or live vaccine within 4 weeks before the first dose of study drug;
15. enrolled in an additional clinical trial within 4 weeks before initiation of treatment.

Where this trial is running

Chengdu, Sichuan

• West China Hospital — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Study coordinator: Wang Ziqiang, PhD

Conditions Rectal Cancer