Advanced intrahepatic cholangiocarcinoma
Conditions
Interventions
Experimental group (Phase I):This phase is a single-arm, open design and is intended to determine the MTD and/or RP2D of doxycycline by dose climbing (200mg/ day, 400mg/ day, 600mg/ day, 800mg/ day).
Experimental group (Phase II):This stage is to preliminarly observe the efficacy of doxycycline in the treatment of patients with intrahepatic cholangiocarcinoma who are unresponsive or resistant to c
Sponsors
The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: • Gender, age 18-75 years old; • The subject or guardian understands and voluntarily signs the informed consent, and has the willingness and ability to complete the regular visits, treatment plans, laboratory examinations, etc. required by the program; • The subject is not suitable for radical excision, transplantation or ablation, including recurrence after radical resection is not suitable for further radical excision or ablation; • Expected survival of more than 12 weeks; • no radiation therapy within 12 weeks prior to initial dosing; • CCA meets AASLD or EASL clinical diagnostic criteria; • CCA is not feasible for surgical resection or distant metastasis, and progresses after first-line chemotherapy combined with PD-1 monoclonal antibody treatment; • No response or drug resistance to chemotherapy combined with PD-1 monoclonal antibody; • Liver function Child-Pugh grade A or B with a score of 7; • ECOG score 0-1; • Platelet count =60×109/L, PT time extension =6 seconds.
Exclusion criteria
Exclusion criteria: • uncorrectable coagulation dysfunction, with a significant bleeding tendency; • Patients who require long-term anticoagulant and antiplatelet therapy and cannot be stopped; • Patients with current unstable or active ulcers and gastrointestinal bleeding; • Present with heart disease that requires treatment or high blood pressure that the investigator determines is poorly controlled; • Patients with interstitial pneumonia; • Patients with hepatic encephalopathy or refractory ascites requiring treatment; • Other concomitant anti-tumor therapy: small-molecule targeted anti-tumor drugs within 2 weeks, proprietary Chinese medicines with definite anti-tumor therapy within 2 weeks, and PD-1/PD-L1 inhibitors within 3 weeks; • severe liver and kidney dysfunction; • Breastfeeding or pregnant female subjects; • The investigator assessed that the patient was unable or unwilling to comply with the requirements of the study protocol; • Allergic to doxycycline or other tetracycline drugs or excipients. Persistent gastrointestinal disorders (including difficulty swallowing capsules, Crohn's disease, ulcerative colitis, etc.) or other malabsorption conditions that may affect the absorption of oral investigational drugs. • Patients using drugs or herbal supplements known to be CYP3A suppressants or inducers within 2 weeks or 5 half-lives prior to first dosing, whichever is longer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Tolerability;Maximum Tolerated Dose;Recommended Phase II Dose;Progression-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;Pharmacodynamics;Objective Response Rate;Overall Survival; | — |
Countries
China
Contacts
Public ContactZhou Weiping
The Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital)
Outcome results
None listed