SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy for HIgh-Risk pMMR/MSS Rectal Cancer

NCT06908031 | Recruiting Phase 2 DMC

• 1 other identifier: E2025076
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the efficacy and safety of short-course radiotherapy combined with mFOLFOX6, PD-1 monoclonal antibody and cetuximab (for RAS/BRAF Wild-Type)/bevacizumab (for RAS/BRAF Mutant) in High-Risk pMMR/MSS Rectal Adenocarcinoma through a prospective study, providing high-level evidence-based medical evidence for the use in the treatment of high-risk rectal cancer.

Conditions

Rectal Adenocarcinoma; High-Risk Cancer; MSS

Keywords

Short-Course Radiotherapy; Targeting Therapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• pCR rate

  pathological complete response rate

  1 year

Secondary Outcomes (6)

• 3 years DFS Rate

  3 years

• 3 years OS rate

  3 years

• 3 years DMFS Rate

  3 years

• 3 years RFS Rate

  3 years

• R0 resection rate

  1 year

Study Arms (1)

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

EXPERIMENTAL

The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with four cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody, and molecularly targeted drugs (selected based on RAS status; patients with RAS/BRAF wild-type receive cetuximab, while those with RAS/BRAF mutations receive bevacizumab). After completing the first cycle of mFOLFOX6 chemotherapy combined with targeted and immune therapy, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients continue with three additional cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and targeted drugs (bevacizumab is not used in the last cycle of the bevacizumab group). Surgery is performed 8-10 weeks after the completion of SCRT.

Radiation: Short-Course Radiotherapy; Drug: PD-1 monoclonal antibody; Drug: mFOLFOX6 regimen; Drug: Cetuximab; Drug: Bevacizumab; Procedure: Surgical resection

Interventions

Short-Course Radiotherapy RADIATION

Patients undergo SCRT at a dose of 5Gy × 5 fractions

Also known as: SCRT

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

PD-1 monoclonal antibody DRUG

Patients complete immune therapy with PD-1 monoclonal antibody for 4 cycles.

Also known as: PD-1

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

mFOLFOX6 regimen DRUG

Patients complete chemotherapy with mFOLFOX6 regimen for 4 cycles.

Also known as: mFOLFOX6

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

Cetuximab DRUG

Patients with RAS/BRAF wild-type receive targeting therapy with Cetuximab for 4 cycles.

Also known as: Cetuximab Antibody

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

Bevacizumab DRUG

Patients with RAS/BRAF mutations receive targeting therapy with Bevacizumab for 3 cycles. (Bevacizumab is not used in the last cycle of the bevacizumab group)

Also known as: Bevacizumab Antibody

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

Surgical resection PROCEDURE

Surgery either local excition or total mesorectal excision is performed 8-10 weeks after the completion of short-course radiotherapy.

Also known as: Surgery

SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18-75 years.
• Histologically or cytologically confirmed pMMR/MSS rectal adenocarcinoma; all other histological types are excluded.
• Distance from the lower margin of the rectal tumor to the anal verge ≤10 cm.
• Clinical staging with high-risk factors, including cT3Nx, EMVI(+), or cT4, ±MRF(+), ±EMVI(+).
• No evidence of distant metastasis before treatment.
• No prior anti-cancer treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
• ECOG performance status of 0-1.
• Peripheral blood counts and liver and kidney function within the following allowable ranges (tested within 15 days before the start of treatment):
• White blood cells (WBC) ≥3.0×10\^9/L or absolute neutrophil count (ANC) ≥1.5×10\^9/L;
• Hemoglobin (HGB) ≥80 g/L;
• Platelets (PLT) ≥100×10\^9/L;
• Liver transaminases (AST/ALT) \<3.0 times the upper limit of the normal range;
• Total bilirubin (TBIL) \<1.5 times the upper limit of the normal range;
• Creatinine (CREAT) \<1.5 times the upper limit of the normal range.

You may not qualify if:

• Patients with a history of severe drug allergies (including allergies to platinum agents, 5-FU, LV, and 5-HT3 receptor antagonists);
• Patients who have participated in or are currently participating in other clinical trials within 4 weeks prior to enrollment;
• 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;
• Severe electrolyte abnormalities;
• 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;
• 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;
• 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;
• 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);
• 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;
• Patients with active infections (infections causing fever above 38°C);
• Patients with uncontrolled hypercalcemia, hypertension, or diabetes;
• Patients with severe pulmonary diseases (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.);
• Patients with psychiatric disorders that may affect clinical treatment or a history of central nervous system diseases;
• Patients with severe complications (bowel obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.);
• Presence of any CTCAE Grade 2 or higher toxicity caused by previous treatments that has not resolved (excluding anemia, alopecia, and skin pigmentation);

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510065, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

spartalizumab; Cetuximab; Bevacizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Juan Huang, PhD.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Huang, PhD.

CONTACT

+8613926451242; huangj97@mail.sysu.edu.cn

Fang He, MD.

CONTACT

+8618826059789; hefang23@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The neoadjuvant treatment phase includes short-course radiotherapy (SCRT) combined with four cycles of the mFOLFOX6 regimen, PD-1 monoclonal antibody, and molecularly targeted drugs (selected based on RAS status; patients with RAS/BRAF wild-type receive cetuximab, while those with RAS/BRAF mutations receive bevacizumab). After completing the first cycle of mFOLFOX6 chemotherapy combined with targeted and immune therapy, patients undergo SCRT at a dose of 5Gy × 5 fractions. At least 7 days after the completion of radiotherapy, patients continue with three additional cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and targeted drugs (bevacizumab is not used in the last cycle of the bevacizumab group). Surgery is performed 8-10 weeks after the completion of SCRT

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 3, 2025
• Study Start: April 2, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 14, 2025

Record last verified: 2025-04

Locations

CN (1)