HAIC With Oxaliplatin, 5-FU and Bevacizumab Plus Intravenous Toripalimab for Advanced BTC

NCT ID: NCT04217954

Last Updated: 2023-06-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-28

Study Completion Date

2023-06-01

Brief Summary

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Hepatic arterial infusion chemotherapy (HAIC) deliver high concentration of chemotherapeutic agents directly to the liver tumor, was proved to be effective for intrahepatic and perihilar cholangiocarcinoma. Based on the potential synergistic effect of bevacizumab, chemotherapy and PD-1 inhibitor, this phase II clinical study want to test the efficacy and safety using intra-arterial infusion of oxaliplatin, 5-fluorouracil and bevacizumab combined with intravenous infusion of PD-1 inhibitor (Toripalimab) in the treatment of unresectable biliary malignant tumors.

Detailed Description

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Conditions

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Advanced Biliary Tract Cancer

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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OXA, 5-FU and Bev plus Toripalimab

the patients enrolled in this arm would receive hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab

Group Type EXPERIMENTAL

OXA, 5-FU and bevacizumab plus Toripalimab

Intervention Type DRUG

1. concomitant treatment: A. HAIC: oxaliplatin (40 mg/m2 for 2 hours), 5-fluorouracil (800 mg/ m2 for 22 hours) on days 1-3, and arterial bevacizumab 300mg for 2 hours on d1 before oxaliplatin through a percutaneously implanted port-catheter system.

B. Intravenous PD-1 inhibitor (Toripalimab) 240 mg for 30-60 minutes on d1 before the HAIC.

The concomitant treatment repeat every three week, up to 6 cycles.
2. Maintenance treatment: Bevacizumab (300mg) + PD-1 inhibitor (Toripalimab 240mg) will be given intravenously, every 3 weeks.

Interventions

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OXA, 5-FU and bevacizumab plus Toripalimab

1. concomitant treatment: A. HAIC: oxaliplatin (40 mg/m2 for 2 hours), 5-fluorouracil (800 mg/ m2 for 22 hours) on days 1-3, and arterial bevacizumab 300mg for 2 hours on d1 before oxaliplatin through a percutaneously implanted port-catheter system.

B. Intravenous PD-1 inhibitor (Toripalimab) 240 mg for 30-60 minutes on d1 before the HAIC.

The concomitant treatment repeat every three week, up to 6 cycles.
2. Maintenance treatment: Bevacizumab (300mg) + PD-1 inhibitor (Toripalimab 240mg) will be given intravenously, every 3 weeks.

Intervention Type DRUG

Other Intervention Names

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FOLFOX

Eligibility Criteria

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Inclusion Criteria

1. Biliary tract cancer proved by histology or cytology
2. Metastatic advanced or locally advanced unresectable biliary tract cancer, including gallbladder cancer, intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist.
3. At least one measurable lesion within liver;
4. No prior intra-arterial/systemic chemotherapy or other systemic therapies
5. Prior resection, TACE or ablation will be allowed.
6. Age from 18 years old to 80 years old.
7. the performance of Eastern Cooperative Oncology Group (ECOG) \<2
8. Child-Pugh A or Child-Pugh B (≤ score 7).
9. Expectant survival time ≥ 3 months.
10. Baseline blood count test and blood biochemical must meet following criteria:

1. Hemoglobin ≥ 90 g/L;
2. Absolute neutrophil count ≥ 1.5×10\^9/L;
3. Blood platelet count ≥ 100×10\^9/L;
4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal (ULN);
5. Total bilirubin ≤ 2 times of ULN;
6. Serum creatinine ≤ 1.5 times of ULN;
7. Albumin ≥ 30 g/L.
11. Patients sign informed consent.

Exclusion Criteria

1. Distal cholangiocarcinoma.
2. Allergic to contrast agent.
3. Pregnant or lactational.
4. Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil.
5. More than 80 years old.
6. Previous systematic chemotherapy or radiotherapy.
7. Child-Pugh C or Child-Pugh B (≥ score 8).
8. Coinstantaneous a lot of malignant hydrothorax or ascites.
9. History of organ transplantation (including bone marrow auto-transplantation and peripheral stem cell transplantation).
10. Coinstantaneous infection and need anti-infection therapy.
11. Hepatitis B virus DNA load ≥ 100 IU/ml (patients whose hepatitis B virus DNA load decreased to \< 100 IU/ml after anti-virus therapy could be enrolled).
12. Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder.
13. Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.
14. Without legal capacity.
15. Impact the study because of medical or ethical reasons.
16. Uncorrectable coagulation disorder.
17. Obvious abnormal in ECG or obvious clinical symptoms of heart disease, like congestive heart failure (CHF), coronary heart disease with obvious clinical symptoms, unmanageable arrhythmia and hypertension.
18. History of myocardial infarction within 12 months, or Grade III/IV of heart function.
19. Severe liver disease (like cirrhosis), renal disease, respiratory disease, unmanageable diabetes or other kinds of systematic disease.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University

OTHER

Sponsor Role lead

Responsible Party

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Xiaodong Wang, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xiaodong Wang, MD

Role: STUDY_DIRECTOR

Department of Interventional Therapy, Peking University Cancer Hospital

Locations

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Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

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China

References

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Park J, Kim MH, Kim KP, Park DH, Moon SH, Song TJ, Eum J, Lee SS, Seo DW, Lee SK. Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver. 2009 Dec;3(4):298-305. doi: 10.5009/gnl.2009.3.4.298. Epub 2009 Dec 31.

Reference Type BACKGROUND
PMID: 20431764 (View on PubMed)

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

Reference Type BACKGROUND
PMID: 20375404 (View on PubMed)

Boehm LM, Jayakrishnan TT, Miura JT, Zacharias AJ, Johnston FM, Turaga KK, Gamblin TC. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015 Feb;111(2):213-20. doi: 10.1002/jso.23781. Epub 2014 Sep 1.

Reference Type BACKGROUND
PMID: 25176325 (View on PubMed)

Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma. Radiology. 2017 May;283(2):580-589. doi: 10.1148/radiol.2016160572. Epub 2016 Nov 7.

Reference Type BACKGROUND
PMID: 27820684 (View on PubMed)

Gao F, Yang C. Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic. Curr Cancer Drug Targets. 2020;20(1):3-18. doi: 10.2174/1568009619666191114110359.

Reference Type BACKGROUND
PMID: 31729943 (View on PubMed)

Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol. 2018 Oct;52(Pt 2):117-124. doi: 10.1016/j.semcancer.2017.12.002. Epub 2017 Dec 8.

Reference Type BACKGROUND
PMID: 29229461 (View on PubMed)

Mathew M, Enzler T, Shu CA, Rizvi NA. Combining chemotherapy with PD-1 blockade in NSCLC. Pharmacol Ther. 2018 Jun;186:130-137. doi: 10.1016/j.pharmthera.2018.01.003. Epub 2018 Jan 31.

Reference Type BACKGROUND
PMID: 29352857 (View on PubMed)

Dalgleish AG. Rationale for combining immunotherapy with chemotherapy. Immunotherapy. 2015;7(3):309-16. doi: 10.2217/imt.14.111.

Reference Type BACKGROUND
PMID: 25804482 (View on PubMed)

Longo V, Brunetti O, Azzariti A, Galetta D, Nardulli P, Leonetti F, Silvestris N. Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review. Cancers (Basel). 2019 Apr 15;11(4):539. doi: 10.3390/cancers11040539.

Reference Type BACKGROUND
PMID: 30991686 (View on PubMed)

Other Identifiers

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FIBTC

Identifier Type: -

Identifier Source: org_study_id

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