Neoadjuvant treatment for resectable intrahepatic cholangiocarcinoma

A Randomized Controlled, Multicenter, Open, Seamless Phase II-III Clinical Trial of PD1 Antibody (Toripalimab), Lenvatinib and GEMOX Neoadjuvant Treatment for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors

This study is testing a new treatment combining a PD1 antibody, Lenvatinib, and chemotherapy before surgery to see if it helps patients with a specific type of liver cancer have better outcomes and lower chances of the cancer coming back.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 178 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Shanghai Zhongshan Hospital (other)
• Drugs / interventions: lenvatinib, chemotherapy, prednisone, Toripalimab, leventinib
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT04669496 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a combination of PD1 antibody (Toripalimab), Lenvatinib, and GEMOX chemotherapy as neoadjuvant treatment for patients with resectable intrahepatic cholangiocarcinoma who have high-risk factors for recurrence. The study is designed as a randomized controlled, multicenter, open-label trial comparing this new treatment approach to traditional surgical methods. The goal is to improve postoperative outcomes and survival rates for patients with this aggressive form of cancer. Participants will receive the neoadjuvant therapy before surgery to potentially reduce tumor size and recurrence risk.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with histopathologically confirmed resectable intrahepatic cholangiocarcinoma and high-risk recurrence factors.

Not a fit: Patients with unresectable intrahepatic cholangiocarcinoma or those with significant comorbidities that prevent participation in the trial may not benefit.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and reduce recurrence in patients with high-risk intrahepatic cholangiocarcinoma.

How similar studies have performed: Previous studies have shown promising results with similar neoadjuvant therapies in other cancers, but this specific combination is novel in the context of intrahepatic cholangiocarcinoma.

Eligibility criteria

Inclusion Criteria:

* 1) Sign written informed consent 2) Male or female patients aged 18-70; 3) ECOG score 0 points, Child-Pugh rating A; 4) Clinically diagnosed as ICC as a potential entry, the neoadjuvant group must be histopathologically diagnosed as intrahepatic cholangiocarcinoma before neoadjuvant, and the traditional group must be pathologically confirmed as intrahepatic cholangiocarcinoma after surgery; 5) Resectable ICC patients with high risk factors for recurrence (tumor diameter\>5cm or imaging vascular invasion, multiple tumor nodules or hilar lymph node metastasis or preoperative CA199\>37U/ml); 6) The functional indicators of important organs meet the following requirements

  1. Neutrophils≥1.5\*109/L; platelets≥90\*109/L; hemoglobin≥9g/dl; serum albumin≥3.5g/dl;
  2. Coagulation function: International standardization (prothrombin time) ratio (INR) \<1.2;
  3. T3 and T4 do not exceed the normal upper and lower limits by 2 times;
  4. Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal;
  5. Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥ 60ml/min; 7) The subject has at least 1 measurable liver disease (according to RECIST1.1); 8) For women who are not breastfeeding or pregnant, use contraception during treatment or 3 months after the end of treatment.

Exclusion Criteria:

* 1) Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-biliary cell carcinoma malignant tumor components; 2) Patients who relapse after surgery, have received PD1 antibody, PDL1 antibody or CTLA4 antibody, lenvatinib, chemotherapy in the past; participated in other clinical trials 30 days before screening; 3) Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma; 4) Active tuberculosis infection. Patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, no formal anti-tuberculosis treatment or tuberculosis is still active; 5) Suffer from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only need hormone replacement therapy and skin diseases without systemic therapy can be selected; 6) Past interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy; 7) Long-term use of systemic hormones (dose equivalent to \>10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects using inhaled or topical corticosteroids can be selected; 8) Active infections that require systemic treatment; 9) Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; 10) A history of psychotropic drug abuse, alcohol or drug abuse; 11) Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; 12) Suspected of being allergic to study drugs; 13) Suffer from hypertension, and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); 14) After antiviral therapy, HBvDNA\>104 copies/ml, HCV RNA\>1000; 15) Accompanied by ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc. Combined with insufficiency of other organs, it is expected that they cannot accept general anesthesia or hepatectomy; 16) Other factors judged by the investigator that may affect the safety of the subject or the compliance of the trial. Such as serious illnesses (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Where this trial is running

Shanghai, Shanghai

• Zhongshan hospital — Shanghai, Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Xiao-yong Huang, MD

Conditions: Intrahepatic Cholangiocarcinoma, PD1 Antibody, Lenvatinib, Gemox Chemotherapy