A Study of HA121-28 Tablets in Advanced Biliary Tract Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Multicentre, Open-label, Single-arm Phase II Study of HA121-28 Tablets in Advanced Biliary Tract Cancer (BTC)

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: HA121-28 tablets


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HA121-28 tablets<br>HA121-28 600 mg, po, QD×21 days, every 4 weeks (28 days) | Drug: HA121-28 tablets<br>* HA121-28 600 mg, po, QD×21 days, every 4 weeks (28 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | Approximately 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective remission rate |  | Approximately 3.5 years | 
| overall survival |  | Approximately 3.5 years | 
| disease control rate |  | Approximately 3.5 years | 
| duration of response |  | Approximately 3.5 years |