Apatinib as Second Line Therapy in Patients With Advanced Refractory Biliary Tract Cancers

Phase II Study of Apatinib as Second Line Therapy in Patients With Advanced Refractory Biliary Tract Cancer

This study is designed to see whether Apatinib is effective in treating patients with advanced refractory biliary tract cancers.

Study Overview

• Status: Unknown
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: Apatinib

Detailed Description

Biliary tract cancers (BTC) includes cholangiocarcinoma and gallbladder carcinoma (GBC). The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic BTC. There is no standard recommendation for second line therapy.

Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2).

This study was conducted to assess the efficacy and safety of Apatinib in patients with advanced refractory BTC who had received first-line chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China
      • Recruiting
      • Foshan people's Hospital
      • Contact: Wei Wang; Phone Number: 075783161035; Email: m18038863618@163.com
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer center of Sun Yat-sen University
      • Contact: Miao-Zhen Qiu, MD, PhD; Phone Number: 86-020-87342490; Email: qiumzh@sysucc.org.cn
      • Contact: Fenghua Wang, MD, PhD; Phone Number: 86-020-87342490; Email: wangfh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must have histologically or cytologically documented carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder with clinical and/or radiologic evidence of unresectable, locally advanced or metastatic disease.
2. Patients with ampullary carcinoma are not eligible.
3. Must have failed or are intolerant to one line of systemic treatment but no more than 2 prior lines of systemic chemotherapy for advanced BTC. Patients who received adjuvant chemotherapy and had evidence of disease recurrence within 6 months of completion of the adjuvant treatment are also eligible. If the patient received adjuvant treatment and had disease recurrence after 6 months, patients will only be eligible after failing or having intolerance to one line of systemic chemotherapy used to treat the disease recurrence.
4. Age between 18 and 75 years old
5. Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1.
6. Must have radiographic measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
7. Life expectancy of at least 12 weeks (3 months).
8. For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: 28 days have elapsed since that therapy; Lesions that have not been treated with local therapy must be present and measureable.
9. Must be able to understand and be willing to sign the written informed consent form. Must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study requirements.
10. All acute toxic effects of any prior treatment have resolved to NCI-CTCAE v4.0 Grade 1 or less at the time of signing the Informed Consent Form (ICF) except for alopecia.
11. Adequate bone marrow, liver and liver function.
12. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug.
13. Men and women of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 3 months after the last dose of study drug.

Exclusion Criteria:

1. Pregnant or lactating women;
2. History of other malignancies except cured basal cell carcinoma of skin and carcinoma insitu of uterine cervix;
3. Uncontrolled hypertension;
4. Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure;
5. Urine protein>grade 1;
6. Any factors that influence the usage of oral administration;
7. Patients with a clear tendency of gastrointestinal bleeding;
8. Abnormal coagulation function(INR≥1.5, APTT≥1.5 ULN);
9. Abuse of alcohol or drugs;
10. Less than 4 weeks from the last clinical trial;
11. Prior treatment with antivascular endothelial growth factor or the other anti angiogenesis therapy;
12. Active central nervous system (CNS). If CNS metastases are treated and potential participants are at neurologic baseline for at least 2 weeks prior to enrollment, they will be eligible but will need a Brain MRI prior to enrollment. 13. Disability of serious uncontrolled intercurrence infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apatinib group; Apatinib 500mg, po, QD, every 4 weeks.	Drug: Apatinib; Apatinib 500mg, po, qd, every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	the time from randomize to progression or death; RECIST guidelines were used to define all responses after patients had received every 4 weeks of therapy	Approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from randomize to death	Approximately 2 years
Disease control rate(DCR)	Defined as the rate of complete response , partial response and stable disease according to RECIST guidelines	Approximately 1 year
Quality of life(QoL)	As measured by the European Organization for Research and Treatment of Cancer questionnaire (EORTC QLQ C30)	Approximately 1 year
Safety (incidence of adverse events)	Incidence of adverse events	Approximately 1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Rui-hua Xu, MD, PhD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2017
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Apatinib; Biliary Tract Cancer; Second line thrapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: Apatinib_BTC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No