Combining radiotherapy and immunotherapy for high-risk rectal cancer

Short-Course Radiotherapy Combined With mFOLFOX6, PD-1 Antibody and Cetuximab (for RAS/BRAF Wild-Type)/Bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma: a Prospective, Multicenter Phase II Study

This study is testing a new treatment combining radiation, chemotherapy, and targeted therapies to see if it helps people with high-risk rectal cancer respond better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy, cetuximab, bevacizumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06908031 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness and safety of a treatment regimen that includes short-course radiotherapy, mFOLFOX6 chemotherapy, and PD-1 monoclonal antibodies combined with targeted therapies for patients with high-risk locally advanced rectal adenocarcinoma. The aim is to improve the pathological complete response rate and enhance long-term survival outcomes for patients with specific high-risk factors. The study is designed as a prospective, open-label, multicenter, single-arm trial to gather high-level evidence for this comprehensive treatment approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed pMMR/MSS rectal adenocarcinoma and specific high-risk clinical staging.

Not a fit: Patients with distant metastasis or those who have received prior anti-cancer treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and treatment outcomes for patients with high-risk rectal cancer.

How similar studies have performed: While this approach combines established therapies, the specific combination and its application in this high-risk group may be novel and untested.

Eligibility criteria

Inclusion Criteria:

1. Before conducting procedures related to the research protocol but not part of routine care, written informed consent, voluntarily signed and dated by the subject, must be obtained in accordance with regulations and institutional guidelines.
2. Age 18-75 years.
3. Histologically or cytologically confirmed pMMR/MSS rectal adenocarcinoma; all other histological types are excluded.
4. Distance from the lower margin of the rectal tumor to the anal verge ≤10 cm.
5. Clinical staging with high-risk factors, including cT3Nx, EMVI(+), or cT4, ±MRF(+), ±EMVI(+).
6. No evidence of distant metastasis before treatment.
7. No prior anti-cancer treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
8. ECOG performance status of 0-1.
9. Peripheral blood counts and liver and kidney function within the following allowable ranges (tested within 15 days before the start of treatment):

   1. White blood cells (WBC) ≥3.0×10\^9/L or absolute neutrophil count (ANC) ≥1.5×10\^9/L;
   2. Hemoglobin (HGB) ≥80 g/L;
   3. Platelets (PLT) ≥100×10\^9/L;
   4. Liver transaminases (AST/ALT) \<3.0 times the upper limit of the normal range;
   5. Total bilirubin (TBIL) \<1.5 times the upper limit of the normal range;
   6. Creatinine (CREAT) \<1.5 times the upper limit of the normal range.
10. No history of other malignancies; not pregnant or breastfeeding, and effective contraception must be used during the study period and for 6 months after the last dose.

Exclusion Criteria:

1. Patients with a history of severe drug allergies (including allergies to platinum agents, 5-FU, LV, and 5-HT3 receptor antagonists);
2. Patients who have participated in or are currently participating in other clinical trials within 4 weeks prior to enrollment;
3. A history of having received anti-PD-1, PD-L1, PD-L2, CTLA-4, or any other specific T-cell costimulatory or checkpoint pathway-targeted therapy;
4. Severe electrolyte abnormalities;
5. Presence of gastrointestinal diseases, such as active ulcers in the stomach or duodenum, ulcerative colitis, or tumors with active bleeding that have not been resected; or other conditions that may lead to gastrointestinal bleeding or perforation; or gastrointestinal perforation that has not healed after surgical treatment;
6. History of arterial thrombosis or deep vein thrombosis within 6 months; history of bleeding or evidence of bleeding tendency within 2 months; or patients receiving high-dose anticoagulation therapy;
7. Pregnant or breastfeeding women, or women of childbearing potential with a positive pregnancy test before the first dose; or female participants and their partners who are unwilling to strictly practice contraception during the study period;
8. Presence of other active malignancies (except for malignancies that have been treated with curative intent and have been disease-free for more than 3 years, or in situ cancers that can be cured with adequate treatment);
9. Presence of severe ECG abnormalities or active coronary artery disease, severe/unstable angina, newly diagnosed angina or myocardial infarction within 12 months prior to study entry, or New York Heart Association (NYHA) Class II or higher congestive heart failure;
10. Patients with active infections (infections causing fever above 38°C);
11. Patients with uncontrolled hypercalcemia, hypertension, or diabetes;
12. Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
13. Patients with psychiatric disorders that may affect clinical treatment or a history of central nervous system diseases;
14. Patients with severe complications (bowel obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.);
15. Presence of any CTCAE Grade 2 or higher toxicity caused by previous treatments that has not resolved (excluding anemia, alopecia, and skin pigmentation);
16. Any unstable medical condition that may affect patient safety and compliance with the study;
17. Patients deemed by the investigator as unsuitable for participation in this clinical trial.

Where this trial is running

Guangzhou, Guangdong

• Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Juan Huang, PhD. — Sun Yat-sen University
• Study coordinator: Jun Huang, PhD.

Conditions: Rectal Adenocarcinoma, High-Risk Cancer, MSS, Short-Course Radiotherapy, Targeting Therapy, Immunotherapy