Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer

Cholangiocarcinoma Clinical Trial

— LENABC  

Official title:

The Efficacy and Safety of Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04656249
• Other study ID #: PUMCH-JS-1391
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2018
• Est. completion date: May 1, 2021

Study information

• Verified date: November 2020
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, nonrandom, open-label study aiming to evluate the efficacy and safety of lenvatinib for patients with pretreated advanced biliary tract cancer.

Description:

Lenvatinib targets VEGFR1, 2, and 3, PDGFRα, Fibroblast growth factor receptor (FGFR), and the KIT and RET tyrosine kinases and was initially developed for use in various tumor types. This is a single-center, non-random, open-label study in participants with unresectable BTC and disease progression or failure following at least one chemotherapy regimen. This study contains three procedures: a pre-treatment procedure that will last within 21 days; a treatment procedure that will consist of study treatment cycles and tumor assessment conducted every 6-8 weeks; and a follow-up procedure that will begin immediately after the off-treatment visit and will continue as long as the participant is alive, unless the participant withdraws consent, or until the terminal of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: May 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Inclusion Criteria:

1. Pathologically or cytologically confirmed adenocarcinoma of biliary tract cancer (intrahepatic, extrahepatic cholangiocarcinoma, gall bladder cancer), at least one prior chemotherapy.

2. Participants who received adjuvant chemotherapy are eligible if this therapy was completed and recurrent has not been shown for 6 months after the completion of the therapy

3. Measurable disease meeting the following criteria: At least 1 lesion of = 1.0 cm in the longest diameter for a non-lymph node or = 1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1) using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

5. Survival expectation of 3 months or longer after beginning of study treatment

6. Males or females age = 18 years at the time of informed consent

7. All chemotherapy- or radiation-related toxicities must have resolved to Grade 0-1 per Common Terminology Criteria for Adverse Events (CTCAE v 4.03), except alopecia, infertility, and the adverse events listed in inclusion criteria

8. Adequately controlled blood pressure (BP) with or without antihypertensive medications (defined as BP = 150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week prior to the first dose of study drug)

9. Participants with adequate function of major organs and blood coagulation:

10. Absolute neutrophil count (ANC) = 1500/mm^3 ( = 1.5×103/µl); Platelets = 100,000/mm3 ( = 100×10^9/L); Hemoglobin = 9.0 g/dL; Bilirubin = 2.0 mg/dL except for unconjugated hyperbilirubinemia or Gilbert's syndrome; Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) = 3.0 × upper limit of normal (ULN) ( = 5.0 × ULN for participants with the liver metastasis); Creatinine clearance = 40 mL/min per the Cockcroft and Gault formula; Prothrombin time-International Normalized Ratio (PT-INR) = 1.5;

11. Participants must voluntarily agree to provide written informed consent;

12. Participants must be willing and able to comply with all aspects of the protocol

Exclusion Criteria:

1. Ascites of moderate, severe, or requiring drainage

2. Proteinuria of = 2+ on dipstick testing (Grade = 1 confirmed by quantitative assessment is eligible)

3. Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug

4. New York Heart Association congestive heart failure of class II or above, unstable angina, myocardial infarction, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months from the first dose of study drug

5. A prolonged QT/QTc interval (QTcF > 480 ms)

6. Known to be human immunodeficiency virus (HIV) positive

7. Active infection requiring systemic treatment

8. Bleeding or thrombotic disorders or chronic systemic use of anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents (treatment with low molecular weight heparin is permitted)

9. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 21 days prior to the first dose of study drug Active malignancy (except for BTC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ of the cervix, or early stage gastric/colorectal cancer) within the past 24 months prior to the first dose of study drug

10. Known intolerance to the study drug or any of the excipients

11. History of drug or alcohol dependency or abuse within the last 24 months prior to the first dose of study drug

12. Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study

13. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive human chorionic gonadotropin [hCG or B-hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 3 days before the first dose of study drug.

14. For either males unless undergoing a successful vasectomy (confirmed azoospermia) or females of childbearing potential, the participant and his/her partner do not agree to use a medically appropriate method of contraception throughout the entire study period

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms
• Cholangiocarcinoma
• Targeted Therapy

Intervention

Drug:
• Lenvatinib
Drug doses for BTC are identical, being orally administered at 8mg/d to patients weighing <60 kg and 12mg/d to those =60 kg.

Locations

Country	Name	City	State
China	Chinese Academy of Medical Sciences & Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (22)

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Ghidini M, Pizzo C, Botticelli A, Hahne JC, Passalacqua R, Tomasello G, Petrelli F. Biliary tract cancer: current challenges and future prospects. Cancer Manag Res. 2018 Dec 28;11:379-388. doi: 10.2147/CMAR.S157156. eCollection 2019. Review. — View Citation

Hiraoka A, Kumada T, Kariyama K, Takaguchi K, Atsukawa M, Itobayashi E, Tsuji K, Tajiri K, Hirooka M, Shimada N, Shibata H, Ishikawa T, Ochi H, Tada T, Toyoda H, Nouso K, Tsutsui A, Itokawa N, Imai M, Joko K, Hiasa Y, Michitaka K; Real-life Practice Exper — View Citation

Ji X, Bu ZD, Yan Y, Li ZY, Wu AW, Zhang LH, Zhang J, Wu XJ, Zong XL, Li SX, Shan F, Jia ZY, Ji JF. The 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system for gastric cancer is superior to the 7th edition: results fr — View Citation

Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment o — View Citation

Marquardt JU, Saborowski A, Czauderna C, Vogel A. The Changing Landscape of Systemic Treatment of Advanced Hepatocellular Carcinoma: New Targeted Agents and Immunotherapies. Target Oncol. 2019 Apr;14(2):115-123. doi: 10.1007/s11523-019-00624-w. Review. — View Citation

Matsuki M, Hoshi T, Yamamoto Y, Ikemori-Kawada M, Minoshima Y, Funahashi Y, Matsui J. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signaling pathways in human hepatocellular carcinoma models. Cancer Med. 2018 Jun;7(6):2641-2653. doi — View Citation

Obi S, Sato T, Sato S, Kanda M, Tokudome Y, Kojima Y, Suzuki Y, Hosoda K, Kawai T, Kondo Y, Isomura Y, Ohyama H, Nakagomi K, Ashizawa H, Miura Y, Amano H, Mochizuki H, Omata M. The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in — View Citation

Snyder A, Morrissey MP, Hellmann MD. Use of Circulating Tumor DNA for Cancer Immunotherapy. Clin Cancer Res. 2019 Dec 1;25(23):6909-6915. doi: 10.1158/1078-0432.CCR-18-2688. Epub 2019 Jul 8. Review. — View Citation

Sohal DP, Mykulowycz K, Uehara T, Teitelbaum UR, Damjanov N, Giantonio BJ, Carberry M, Wissel P, Jacobs-Small M, O'Dwyer PJ, Sepulveda A, Sun W. A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Ann Oncol. 2013 De — View Citation

Ueno M, Ikeda M, Sasaki T, Nagashima F, Mizuno N, Shimizu S, Ikezawa H, Hayata N, Nakajima R, Morizane C. Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results. BMC Cancer. 2020 Nov — View Citation

Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New Horizons for Precision Medicine in Biliary Tract Cancers. Cancer Discov. 2017 Sep;7(9):943-962. doi: 10.1158/2159-8290.CD-17-0245. Epub 2017 Aug 17. Review. — View Citation

Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, Arén Frontera O, Gettinger S, Holgado E, Spigel D, Waterhouse D, Domine M, Garassino M, Chow LQM, Blumenschein G Jr, Barlesi F, Coudert B, Gainor J, Arrieta O, Brahmer J, Butts C, Steins M, Geese — View Citation

Wang D, Lin J, Yang X, Long J, Bai Y, Yang X, Mao Y, Sang X, Seery S, Zhao H. Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies. J Hematol Oncol. 2019 Apr 24;12(1):42. doi: 10.1186/s13045-019-0730-9. Revie — View Citation

Witjes CD, Karim-Kos HE, Visser O, de Vries E, IJzermans JN, de Man RA, Coebergh JW, Verhoef C. Intrahepatic cholangiocarcinoma in a low endemic area: rising incidence and improved survival. HPB (Oxford). 2012 Nov;14(11):777-81. doi: 10.1111/j.1477-2574.2 — View Citation

Zhang B, Zhang B, Zhang Z, Huang Z, Chen Y, Chen M, Bie P, Peng B, Wu L, Wang Z, Li B, Fan J, Qin L, Chen P, Liu J, Tang Z, Niu J, Yin X, Li D, He S, Jiang B, Mao Y, Zhou W, Chen X. 42,573 cases of hepatectomy in China: a multicenter retrospective investi — View Citation

Zhou J, Sun HC, Wang Z, Cong WM, Wang JH, Zeng MS, Yang JM, Bie P, Liu LX, Wen TF, Han GH, Wang MQ, Liu RB, Lu LG, Ren ZG, Chen MS, Zeng ZC, Liang P, Liang CH, Chen M, Yan FH, Wang WP, Ji Y, Cheng WW, Dai CL, Jia WD, Li YM, Li YX, Liang J, Liu TS, Lv GY, — View Citation

Zhu RX, Seto WK, Lai CL, Yuen MF. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region. Gut Liver. 2016 May 23;10(3):332-9. doi: 10.5009/gnl15257. Review. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical benefit rate (CBR)	Clinical benefit rate (CBR) [ Time Frame: From the date of first dose of study drug to the date of the first documentation of disease progression or death from any cause, whichever occurs first, or up to approximately 1 years ]	One years
Primary	Objective Response Rate (ORR)	Objective response rate	Six months
Primary	Progression free survival (PFS)	Progression free survival	Six months
Secondary	Overall survival (OS)	Overall survival (OS) [ Time Frame: From the date of first dose of study drug to the date of death from any cause, or up to approximately 2 years ]	Two years
Secondary	Disease control rate (DCR)	DCR is defined as the percentage of participants with complete response (CR) + partial response (PR) + stable disease (SD).	Six months
Secondary	The Rate of Treatment Related Adverse Events	Treatment related adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE 4.0). The study recorded the occurrence rate of treatment related AEs	Three years