Combining donafenib and capecitabine for treating high-risk biliary cancer after surgery

Donafenib Combined With Capecitabine for Postoperative Adjuvant Therapy of Biliary Malignant Tumors With High-risk Recurrence Risk: a Multi-center, Randomized Controlled, Phase II Study

This study is testing if combining donafenib with capecitabine can help prevent high-risk biliary cancer from coming back after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06685289 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of donafenib combined with capecitabine as adjuvant therapy for patients who have undergone surgery for biliary malignant tumors and are at high risk of recurrence. Participants will be randomly assigned to receive either the combination treatment or capecitabine alone. The study aims to determine the one-year recurrence-free survival rate among the participants. A total of 70 patients will be included in this phase 2 trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with high-risk biliary malignant tumors who have undergone R0 resection and meet specific clinical criteria.

Not a fit: Patients with recurrent or metastatic disease, or those who have received prior anti-tumor systemic therapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of cancer recurrence in patients with biliary malignancies.

How similar studies have performed: While this approach is being tested in this specific context, similar combinations have shown promise in other cancer treatments, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Patients must sign an informed consent form;
2. Age range: 18-75 years old, both male and female are welcome;
3. ECOG Physical Status Score (PS Score) 0 or 1;
4. Patients with BTC (intrahepatic cholangiocarcinoma ICC; extrahepatic cholangiocarcinoma ECC gallbladder cancer\&hilar cholangiocarcinoma\&distal cholangiocarcinoma) diagnosed by histopathology after resection of specimens, R0 resection and having at least one of the following high-risk recurrence factors;

   1. According to the UICC/AJCC TNM 8th edition staging system: T2-4, N0, M0 or T1-4, N1, M0 (applicable to ECC subjects); T1b-4, N0-1, M0 or T1a, N1, M0 (applicable to ICC subjects); - Please refer to the screenshot level PDF file at the end of the article for the installment standards
   2. Vascular invasion;
   3. Neurophilic invasion (PNI);
5. No recurrence or metastasis on imaging within the first 28 days of randomization;
6. Prior to radical resection, no anti-tumor systemic therapy (including radiotherapy, chemotherapy, targeted therapy, immunotherapy) was received;
7. The laboratory test values within 7 days before the first medication meet the requirements:
8. Expected survival period greater than 6 months;
9. Women with fertility must agree to abstain from sexual intercourse (avoid heterosexual intercourse) or use reliable and effective methods of contraception for at least 120 days from the date of signing the informed consent form until the last administration of the study drug. And the serum HCG test must be negative within 72 hours before randomization; And it must be non lactating.

   If a woman has already menstruated, has not yet reached postmenopausal status (continuous absence of menstruation for ≥ 12 months, no other reasons found besides menopause), and has not undergone sterilization surgery (such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), she is considered to have fertility.
10. For male participants whose partners are fertile women, they must agree to abstain from sexual activity for at least 120 days from the signing of the informed consent form until the last administration of the study drug, or to use reliable and effective methods of contraception. Male participants must also agree not to donate sperm during the same time period. Male participants whose partners are already pregnant are required to use condoms and do not need to use other contraceptive methods.

Exclusion Criteria:

1. Pathological diagnosis of mixed hepatocellular carcinoma and other non cholangiocarcinoma malignant tumor components;
2. Previously received systemic treatment;
3. Previous or concurrent malignant tumors, excluding fully treated non melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
4. Active tuberculosis infection. Patients with active pulmonary tuberculosis infection within the year prior to enrollment; Having a history of active pulmonary tuberculosis infection more than one year prior to enrollment, not receiving formal anti tuberculosis treatment, or having active tuberculosis;
5. History of autoimmune diseases or immunodeficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain Barr é syndrome, or multiple sclerosis;
6. Long term systemic hormone therapy (equivalent to\>10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects who use inhaled or topical corticosteroids may be included;
7. Severe heart, lung, and kidney dysfunction;
8. Insufficient control of arterial hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) (based on the average of BP readings obtained from ≥ 2 measurements), allowing for the use of antihypertensive therapy to achieve the above parameters; Previously experienced hypertensive crisis or hypertensive encephalopathy;
9. Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies; Abnormal coagulation function (PT\>14s), with a tendency towards bleeding or currently undergoing thrombolytic or anticoagulant therapy;
10. HBV DNA\>2000IU/ml, HCV active infection (HCV antibody positive and HCV-RNA level above the detection limit);
11. Active infections that require systemic treatment;
12. Positive for human immunodeficiency virus (HIV, HIV1/2 antibody);
13. Have a history of substance abuse, alcoholism, or drug use;
14. Have a history of researching drug allergies;
15. Other factors that may affect subject safety or trial compliance, as determined by researchers. Serious illnesses (including mental illnesses) that require combined treatment, severe laboratory abnormalities, or other family or social factors.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Jianhua Rao

Conditions Biliary Malignant Tumors