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

Plain English Summary

Umbrella Trial of Neoadjuvant Therapy for Locally Advanced Colorectal Cancer is a Phase 2 clinical trial sponsored by Fudan University studying Locally Advanced Colorectal Cancer. This trial tests different neoadjuvant (pre-surgery) therapies for locally advanced colorectal cancer. It is for patients with stage II or III colon cancer, or stage II or III rectal cancer close to the anus, who have not had prior cancer treatment. Participation involves receiving one of several assigned treatment regimens before surgery, with regular check-ups and tests. Alternatives may include standard surgery, chemotherapy, or radiation without this specialized pre-treatment approach. The trial aims to enroll 134 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18-75 with confirmed colon or rectal cancer (stage II/III) that has not spread to distant parts of the body. Must be healthy enough to undergo treatment, with good performance status (KPS >= 70) and acceptable blood counts. Cannot have received any prior cancer treatments like chemotherapy, radiation, or immunotherapy. Not eligible if pregnant, breastfeeding, have other recent cancers, severe heart/kidney/liver issues, uncontrolled infections, or certain immune conditions. This trial is studying Locally Advanced Colorectal Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see how many patients achieve a complete response, meaning all detectable cancer is gone after treatment, which could lead to better outcomes and potentially less invasive surgery. The specific primary outcome measures are: 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. (1 month after the surgery or 1 year after the decision of W&W.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment outcomes for locally advanced colorectal cancer by matching specific therapies to different molecular subtypes of the disease, addressing a need for more personali Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Locally Advanced Colorectal Cancer, where improved treatment options are needed.

Investor Insight

This trial explores novel combination therapies for a significant cancer market, with potential for improved efficacy and market differentiation if successful, though approval probability depends on r Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific treatment you might receive, potential side effects, and how it could impact your surgery options. Be prepared for regular clinic visits for treatment administration, blood tests, scans, and monitoring. Understand that participation involves receiving treatment before surgery, and the exact regimen will be determined by your cancer's specific characteristics. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 134 participants

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

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. (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. (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. (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. (1 month after the surgery.)
• Rate of surgical complications: rates of surgical complications such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc. (within 3 months after the surgery.)
• Treatment compliance: treatment completion rate and delay duration during the treatment period. (From date of stratification to the completion of neoadjuvant therapy, an average of 5 months.)

Full Eligibility Criteria

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.

Frequently Asked Questions

Related Conditions

• Colorectal Cancer
• Colon Cancer
• Rectal Cancer
• Adenocarcinoma
• Locally Advanced Cancer
• Microsatellite Instability (MSI)
• KRAS Mutation
• Cancer Genomics
• Neoadjuvant Therapy
• Immunotherapy

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