Combination therapy for advanced colorectal cancer

mFOLFOX6 + Bevacizumab + PD-1 Monoclonal Antibody Versus mFOLFOX6 as Neoadjuvant Therapy for Locally Advanced pMMR/MSS Colorectal Cancer: A Prospective, Multicenter, Randomized Phase III Study (BASKETIII)

This study is testing a new combination treatment for people with advanced colorectal cancer to see if it can help them respond better to therapy and live longer compared to a standard treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 166 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Bevacizumab, sintilimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06791512 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a neoadjuvant therapy regimen combining mFOLFOX6, Bevacizumab, and a PD-1 monoclonal antibody in patients with locally advanced pMMR/MSS colorectal cancer. It is a multicenter, randomized phase III study where participants are assigned to either the experimental group receiving the combination therapy or the control group receiving mFOLFOX6 alone. The primary goals are to improve the pathological complete response rates and enhance survival outcomes while managing toxicity levels. The study builds on previous findings that suggested improved immunotherapy sensitivity in this patient population.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed adenocarcinoma of the colon or upper rectum, classified as pMMR/MSS, and staged as cT4NxM0.

Not a fit: Patients with mismatch repair-deficient or microsatellite instability-high colorectal cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and outcomes for patients with locally advanced colorectal cancer.

How similar studies have performed: Previous studies have shown promising results with similar combination therapies in enhancing treatment efficacy for colorectal cancer.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the colon or upper rectum.
2. Tumor biopsy immunohistochemical (IHC) identified pMMR, including all of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as proficient mismatch repair(pMMR), or microsatellite stable (MSS) identified through next-generation sequencing or polymerase chain reaction.
3. Clinical staging of cT4NxM0, with or without positive mesorectal fascia (MRF), and with or without extramural vascular invasion (EMVI); imaging confirms that the lower margin of the tumor is located above the peritoneal reflection (colon or upper rectum).
4. Staging method: All patients must undergo chest, abdominal, and pelvic contrast-enhanced CT, rectal palpation, and high-resolution MRI. Positive perienteric lymph nodes (LNs) are defined as LNs with a short diameter ≥10 mm or LNs exhibiting typical metastatic shape and MRI characteristics. When staging results are contradictory, clinical data must be re-evaluated and confirmed by the central evaluation group. Distant metastases must be excluded through chest and abdominal contrast-enhanced CT and pelvic contrast-enhanced MRI.
5. No symptoms of intestinal obstruction, or obstruction successfully relieved by proximal colostomy.
6. No history of colorectal surgery.
7. No prior chemotherapy or radiotherapy.
8. No history of biopharmaceutical treatments (e.g., monoclonal antibody ), immunotherapy (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies), or treatment with investigational drugs.
9. Endocrine therapy history: Not restricted.
10. Signed informed consent obtained.

Exclusion Criteria:

1. Arrhythmias requiring anti-arrhythmic treatment (except β-blockers or Digoxin), symptomatic coronary artery disease, myocardial ischemia (myocardial infarction within the past 6 months), or congestive heart failure (CHF) \> NYHA Class II.
2. Severe hypertension that is not well controlled by medication.
3. History of HIV infection or active chronic Hepatitis B or C (with high viral DNA load).
4. Active tuberculosis (TB), ongoing anti-TB treatment, or anti-TB treatment within 1 year prior to trial screening.
5. Other active severe infections as defined by NCI-CTCAE v5.0.
6. Evidence of distant metastasis beyond the pelvic region.
7. Blood dyscrasias or organ dysfunction.
8. History of pelvic or abdominal radiotherapy.
9. Multiple colorectal cancer or multiple primary tumors.
10. Epilepsy requiring treatment (e.g., steroids or anti-epileptic drugs).
11. History of other malignancies within the past 5 years.
12. History of drug abuse, or medical, psychological, or social conditions that could interfere with patient participation or the evaluation of study results.
13. Any active autoimmune disease or a history of autoimmune disease (including but not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators).
14. Administration of any live attenuated vaccine within 4 weeks prior to inclusion.
15. Long-term use of immunosuppressants or systemic/topical corticosteroids (dose \>10 mg/day prednisolone or equivalent).
16. Known or suspected allergy to any study-related drug.
17. Any unstable condition that could compromise patient safety or compliance.
18. Pregnant or breastfeeding women, or women of childbearing potential not using effective contraception.
19. Refusal to provide signed informed consent.

Where this trial is running

Guangzhou, Guangdong

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

Study contacts

• Principal investigator: Jun Huang, MD — The Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Jun Huang, MD

Conditions Colorectal Cancer; pMMR/MSS Adenocarcinoma of the Colon or Rectum; Colorectal cancer; pMMR/MSS; Neoadjuvant Therapy; PD-1 monoclonal antibody; mFOLFOX6