Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

Official title

An Exploratory Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer Based on Molecular Subtypes

Overview

This is a prospective, open-label, single-center, phase II umbrella trial designed to evaluate the efficacy and safety of neoadjuvant therapy for locally advanced colorectal cancer. Patients will be stratified into four cohorts based on microsatellite instability (MSI) status, KRAS mutation status, and the consensus molecular subtypes (CMS). Six arms are included across four cohorts and each arm will be assigned to a specific treatment regimen. The primary endpoint is the complete response rate. Secondary endpoints include safety, organ preservation rate (for rectal cancer only), R0 resection rate, surgical complications, treatment compliance, 3-year survival, and quality of life (QoL) score.

Interventions

• Drug SHR-1701
  1800mg d1 q3w
• Drug SHR-8068
  280mg，C1D1
• Radiation Short-course radiotherapy
  25Gy/5Fx
• Drug XELOX (Capecitabine and Oxaliplatin)
  Oxaliplatin: 130mg/m2 d1 q3w Capecitabine: 1000mg/m2 bid d1-14 q3w
• Drug PD-L1 antibody
  1200mg d1 q3w
• Drug cetuximab β
  250mg/m2 d1, 500mg/m2 d8 q3w
• Drug HRS-7058
  200mg bid
• Drug HRS-4642
  500mg d1, 1200mg d8 q3w

Primary outcome measures

• Complete response (CR) rate: rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy. [Time frame: 1 month after the surgery or 1 year after the decision of W&W.]

Secondary outcome measures (10)

• Adverse effects rate: proportion of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0. [Time frame: From date of stratification to 3 months post-neoadjuvant therapy, an average of 8 months.]
• Organ preservation rate: proportion of participants who either achieve cCR and choose W&W or achieve cCR/near-cCR and choose local excision, out of the total participants who complete neoadjuvant therapy. [Time frame: From date of stratification until the resection of rectum or anus, assessed up to 36 months.]
• R0 resection rate: proportion of surgical resections with negative margins (proximal, distal, and circumferential) on microscopic examination, with CRM negativity defined as > 1 mm from tumor bed. [Time frame: 1 month after the surgery.]
• Rate of surgical complications: rates of surgical complications such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. [Time frame: within 3 months after the surgery.]
• Treatment compliance: treatment completion rate and delay duration during the treatment period. [Time frame: From date of stratification to the completion of neoadjuvant therapy, an average of 5 months.]
• 3 year local recurrence free survival rate: proportion of participants with no tumor recurrence in the primary site (e.g., rectum) or other pelvic regions within 3 years from date of surgery or cCR. [Time frame: From date of surgery or cCR until the date of first documented pelvic failure, assessed up to 36 months.]
• 3 year distant metastasis free survival rate: proportion of participants with no distant metastases (e.g., liver, lung) within 3 years from date of stratification. [Time frame: From date of stratification until the date of first documented distant metastasis, assessed up to 36 months.]
• 3 year disease free survival rate: proportion of participants with no disease recurrence (including local recurrence and distant metastasis) or death from the disease within 3 years from date of stratification. [Time frame: From date of stratification until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]
• 3 year overall survival rate: proportion of participants who are alive at 3 years from date of stratification. [Time frame: From date of stratification until the date of death from any cause, assessed up to 36 months.]
• Quality of life (QoL) score: subjective assessment using validated standardized questionnaires. [Time frame: From date of stratification to 3 years post-neoadjuvant therapy.]

Eligibility criteria

Inclusion criteria

• Age 18-75 years old, female and male;
• Pathological confirmed adenocarcinoma;
• Stage II/III colon cancer, or stage II/III rectal cancer located less than 10 cm from the anal verge;
• Treatment-naïve and no distance metastases;
• KPS ≥ 70;
• No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
• Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
• With good compliance and signed the consent form.

Exclusion criteria

• Pregnancy or breast-feeding women;
• Known history of other malignancies within 5 years;
• Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
• Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
• Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
• Uncontrolled infection which needs systemic therapy;
• Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
• Allergic to any component of the therapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07503639 · 2025-697-4846

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗