Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer

Launched by FUDAN UNIVERSITY · Sep 10, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a new treatment called Ivosidenib combined with chemotherapy (CapeOX) and radiotherapy for patients with advanced colorectal cancer that cannot be surgically removed. The goal is to see if this combination can help shrink tumors and improve patient outcomes. Participants in the trial will first receive Ivosidenib along with chemotherapy, followed by targeted radiation therapy to the tumors. After radiation, they will continue with the same medication and chemotherapy until their condition is evaluated. If their cancer shows no signs of disease, some might be eligible for surgery.

To be eligible for this trial, participants must be between 18 and 75 years old, have a confirmed diagnosis of colorectal cancer, and have multiple tumors that cannot be surgically removed. They should also be in generally good health with normal organ function. Participants will be monitored closely for safety throughout the study. It’s important to know that this trial is not currently recruiting participants, and those who qualify will receive comprehensive care from a team of medical professionals.

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Eligibility criteria

• Inclusion Criteria:
• • Aged 18-75.
• • ECOG performance status of 0-1.
• • Initial diagnosis confirmed by colonoscopy and pathology as colorectal adenocarcinoma.
• • Imaging confirmation of multiple measurable metastases, deemed unresectable initially after MDT discussion.
• • No prior treatment or more than 1 year since completion of initial untreated/post-operative adjuvant chemotherapy, and no previous anti-tumor therapy thereafter.
• • With good organ function, without contraindications for surgery or chemotherapy.
• • Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and international normalized ratio (INR) ≤ 1.5 × ULN (if not receiving anticoagulant therapy).
• • Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein quantitative test must show ≤ 1g protein.
• • Left ventricular ejection fraction (LVEF) ≥ 55%. 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) \< 470 msec.
• • Expected survival \> 6 months.
• • Clear status of KRAS, NRAS, BRAF, and HER2 genes.
• • Microsatellite stable or mismatch repair protein proficient patients.
• Exclusion Criteria:
• • Age \<18 years or \>75 years.
• • History of any other malignancy within 5 years, except adequately treated cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that has been effectively controlled.
• • Malignant pleural or peritoneal effusion.
• • Severe internal medical complications preventing chemotherapy or surgery.
• • Clinical or radiological evidence of spinal cord compression, or tumor within 3 mm of the spinal cord on MRI.
• • Imaging-confirmed brain, ovarian, or peritoneal metastases.
• • Patients deemed suitable for aggressive systemic treatment to achieve conversion after MDT discussion.
• • Pathologically diagnosed signet ring cell carcinoma.
• • Patients with microsatellite instability or mismatch repair protein deficiencies.
• • Patients with intestinal obstruction, perforation, bleeding requiring emergency surgical resection.
• • Immunodeficiency diseases, including primary immunodeficiency diseases (genetically determined) or secondary immunodeficiency diseases.
• • Known or suspected interstitial pneumonia.
• • Severe cardiovascular diseases, including but not limited to conditions meeting NYHA class (III or higher), myocardial infarction or cerebrovascular accident (ischemic stroke, symptomatic cerebral infarction) within the past 3 months prior to first dosing, unstable angina or unstable arrhythmias within the past 1 month prior to first dosing, congestive heart failure beyond the above criteria, symptomatic superior vena cava syndrome, etc.
• • Venous thromboembolic events within the past 3 months, such as deep vein thrombosis and pulmonary embolism.
• • History of receiving live attenuated vaccines within 28 days prior to first study drug administration or anticipated need for live attenuated vaccines during the study period.
• • Active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] with HBV-DNA ≥500 IU/ml).
• • Hepatitis C (defined as positive hepatitis C virus antibody \[HCV-Ab\]).
• • History of tuberculosis infection or treatment within the past 1 year prior to signing informed consent.
• • History of or planned allogeneic bone marrow or solid organ transplantation.
• • Abnormal coagulation function (INR \> 1.5 or APTT \> 1.5 × ULN), with bleeding tendency or undergoing thrombolysis or requiring long-term anticoagulant therapy with warfarin or heparin, or requiring long-term antiplatelet therapy (aspirin ≥ 300 mg/day or clopidogrel ≥ 75 mg/day).
• • Peripheral neuropathy of Grade ≥2 according to NCI-CTCAE v5.0.
• • Concurrent other infectious diseases unsuitable for participation in this study.