Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

Phase 2Not Yet RecruitingNCT07503639

Fudan University134 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

134

Conditions

Locally Advanced Colorectal Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 18-75 years old, female and male; 2. Pathological confirmed adenocarcinoma; 3. Stage II/III colon cancer, or stage II/III rectal cancer located less than 10 cm from the anal verge; 4. Treatment-naïve and no distance metastases; 5. KPS ≥ 70; 6. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment; 7. 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; 8. With good compliance and signed the consent form. Exclusion Criteria: 1. Pregnancy or breast-feeding women; 2. Known history of other malignancies within 5 years; 3. Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy); 4. Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction; 5. Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment; 6. Uncontrolled infection which needs systemic therapy; 7. Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents; 8. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection; 9. Allergic to any component of the therapy.

Outcomes

Primary Outcomes

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 Outcomes

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.

This endpoint is applicable only to patients with locally advanced rectal cancer.

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.