Neoadjuvant therapy for advanced rectal cancer using chemotherapy and immunotherapy

CapeOX Combined With Bevacizumab Plus Pembrolizumab as Neoadjuvant Therapy for Microsatellite Stable Locally Advanced Rectal Cancer (COBP)

This study is testing a new combination of chemotherapy and immunotherapy to see if it can help people with advanced rectal cancer before they have surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (other)
• Drugs / interventions: bevacizumab, chemotherapy, immunotherapy, prednisone, pembrolizumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT05585814 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness and safety of a combination treatment involving capecitabine, oxaliplatin, bevacizumab, and pembrolizumab for patients with microsatellite stable locally advanced rectal cancer. It is a prospective, single-arm study that aims to provide neoadjuvant therapy to patients with specific histological and genetic characteristics. The study will assess the response of the cancer to this combination therapy before surgical intervention.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed locally advanced rectal adenocarcinoma who are microsatellite stable and have not received prior treatment for their condition.

Not a fit: Patients with distant metastasis or those who have received prior chemotherapy, targeted therapy, or immunotherapy within specified timeframes may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with locally advanced rectal cancer by enhancing tumor response prior to surgery.

How similar studies have performed: Other studies have shown promise with similar combinations of chemotherapy and immunotherapy in treating advanced cancers, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed rectal adenocarcinoma with cT3+N+M0
* Immunohistochemistry and/or genetic testing confirmed pMMR/MSS
* Initial diagnosed or recurrent patients will be accepted, patients with recurrence should not have received any treatment include chemotherapy, targeted therapy or immunotherapy within 1 month or radiotherapy within 1 year
* Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and haven't received any local treatment.
* Eastern Cooperative Oncology Group (ECOG) 0-1.
* Absence of distant metastasis confirmed by CT, MRI or PET/CT
* Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
* Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.
* Life expectancy\> 3 months
* Signed and written informed consent

Exclusion Criteria:

* Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA4.
* Uncontrolled active bleeding from the primary tumor or intestinal obstruction.
* Contraindications of bevacizumab
* Hypersensitivity to other monoclonal antibodies.
* Any active, known or suspected autoimmune disease.
* Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
* History of one of the following diseases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
* Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
* Active bleeding or abnormal coagulation (aPTT \>43s or INR \>1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
* Previously received allogeneic stem cell or parenchymal organ transplantation.
* Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
* History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
* HIV infection.
* Active hepatitis B or hepatitis C.
* Pregnancy or lactation period, or unwilling to use contraception during the trial.
* With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
* Use corticosteroids (dose of prednisone or similar drugs\> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
* Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
* Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
* Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
* Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
* Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may constrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.

Where this trial is running

Shanghai

• Shanghai Changzheng Hospital — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Haiyang Zhou, MD

Conditions: Locally Advanced Colorectal Cancer