a study of ha121-28 tablets in advanced biliary tract cancer

Conditions: Biliary Tract Cancer

Summary: this study is a multicenter, open-label, single-arm phase ii study to evaluate efficacy, safety, and pharmacokinetics characteristics of ha121-28 tablets in advanced biliary tract cancer (btc). a total of approximately 30 subjects with advanced btc will be enrolled. the subjects will undergo a 3 weeks-on and 1week-off treatment scheme with ha121-28 tablets 600 mg orally once daily in the 28-day cycle until disease progression or intolerable toxic reaction, whichever occurs first.


Eligibility criteria:
inclusion criteria: * be willing to participate in the clinical trial and sign the informed consent; * histologically/cytologically confirmed unresectable locally advanced or metastatic btc (including cholangiocarcinoma or gallbladder cancer) with failure of or intolerance to the prior therapy (including disease progression within 6 months after adjuvant chemotherapy) and with at least one measurable lesion based on recist 1.1 criteria; * aged 18 to 75 years (inclusive); * eastern cooperative oncology group (ecog) performance status of 0\~1; * routine blood test results must meet the following criteria without blood transfusion within 14 days: 1) hemoglobin (hb)≥90 g/l; 2) absolute neutrophil count (anc)≥1.5 x 10\^9/l; 3) platelet count (plt)≥75×10\^9/l; * coagulation test results must meet the following criteria: international normalized ratio (inr) \<1.5 or activated partial thromboplastin time (aptt) \<1.5×uln; * other laboratory test results must meet all the following criteria: 1) total bilirubin (tbil)≤1.5×uln, alanine aminotransferase (alt) and aspartate aminotransferase (ast)≤2.5×uln (tbil≤3×uln, alt and ast≤5×uln in the subjects with liver metastasis); 2) serum creatinine≤1.5×uln；3) serum albumin≥28g/l; * male and female subjects of childbearing potential must agree to take effective contraception for the duration of treatment and for 6 months after completion of study drug administration; female subjects must have negative results of serum/urine pregnancy test within 7 days prior to enrollment and must not be breastfeeding. exclusion criteria: * subjects with ampullary carcinoma; * subjects who had participated in other clinical trials and received the treatment within 4 weeks prior to enrolment; * the time interval between the end of the last antitumor treatment and the first administration of ha121-28 tablets \< 4 weeks (for any antitumor treatment, including but not limited to chemotherapy, radiotherapy and targeted therapy), or \< 2 weeks (for local palliative radiotherapy for pain relief or traditional chinese medicine with approved indications for cancer); * urine protein≥2+ and urine protein \> 1.0g/24h; * history of other malignancies within the past 5 years prior to enrolment, except for cured cervical carcinoma in situ, non-melanoma skin cancer, superficial bladder tumor, and early esophageal and gastrointestinal cancers that were confined to the mucosal layer and resected under endoscopy; * history of any solid-organ or bone-marrow transplantation (except the transplantation without immunosuppression such as corneal and hair transplantation); * unremitted toxic reaction\>grade 1 due to any previous treatment at the time of enrollment (except for hair loss and pigmentation) which is considered to influence the safety evaluation; * ecg meets one of the following criteria: 1) qt/qtc interval≥450ms, congenital long qt syndrome (lqts) or family history of lqts; 2) any clinically significant abnormalities of rhythm, conduction or morphology in the resting ecg requiring therapeutic intervention; * left ventricular ejection fraction (lvef) \<50% in echocardiogram; * severe concomitant diseases which may have influence on the safety of the subjects or the completion of the study based on the investigator' judgement such as uncontrolled hypertension (systolic pressure ≥150 mmhg or diastolic pressure ≥100 mmhg after treatment); * high risk factors of gastrointestinal diseases such as gastrointestinal perforation and abdominal fistula; * subjects with spinal cord, meningeal or brain metastasis (except for asymptomatic or stable brain metastasis within 4 weeks prior to administration); * subjects with hepatopathy meet one of the following criteria: 1) hbsag positive and hbv dna \>2000 iu/ml（or \>1×10\^4 copies/ml）; 2) hcv antibody positive and hcv rna positive; 3) cirrhosis; * hiv antibody positive; * subjects have history of surgery within 4 weeks prior to administration or have not been recovered from any previous invasive procedure, except for biliary stenting, biliary drainage, etc.; * not suitable for the study in the investigator's opinion.