Axitinib Plus Toripalimab as Second-line Treatment in Hepatobiliary Malignant Tumors

NCT04010071 | Unknown Phase 2 DMC

• 1 other identifier: JS-1964
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators design a phase II clinical study to explore the efficacy and safety of axitinib plus toripalimab as a second-line treatment in patients with hepatobiliary malignant tumors and to analyze potential biomarkers of therapeutic response.

Conditions

Hepatobiliary Neoplasm; Liver Neoplasm; Biliary Tract Neoplasms

Keywords

Hepatobiliary Neoplasm; axitinib; toripalimab; biomarker

Outcome Measures

Primary Outcomes (2)

• objective response rate (ORR)

  Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.

  one year

• Progression-free Survival (PFS)

  A duration from the date of initial treatment with axitinib plus toripalimab to disease progression (defined by RECIST 1.1) or death of any cause.

  six months

Secondary Outcomes (6)

• Disease Control Rate (DCR)

  one year

• Overall Survival (OS)

  two years

• Duration of Response (DOR)

  one year

• Stable Disease (SD)

  one year

• Progression free survival rate

  six months

Other Outcomes (3)

• Any adverse events related with treatment with axitinib plus toripalimab.

  one year

• PD-L1 expression

  six months

• Tumor mutation burden

  six months

Study Arms (1)

axitinib plus toripalimab

EXPERIMENTAL

Axitinib (Inlyta, Pfizer Inc.) is a novel oral angiogenesis inhibitor that selectively targets vascular endothelial growth factor (VEGFR) 1, 2 and 3. Toripalimab (Shanghai Junshi Biosciences Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody.

Drug: axitinib plus toripalimab

Interventions

axitinib plus toripalimab DRUG

Axitinib 5mg, twice a day, orally, 4 weeks a cycle. Dose reduction from 5mg twice a day to 3mg twice a day should be considered according to adverse events. Toripalimab 240mg, every 3 weeks, intravenous infused, 6 weeks a cycle. Number of cycle: until disease progression or unacceptable toxicity events.

axitinib plus toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects volunteer to participate in the study and agree to sign the informed consent with good compliance and follow-up.
• Subjects are 18 years old or older when signing the informed consent and gender is not limited.
• Subjects were diagnosed with advanced hepatobiliary malignant tumors (clinical stage IV) by imaging and histological examination, including hepatocellular carcinoma, cholangiocarcinoma, ampullary carcinoma, gallbladder carcinoma and mixed carcinoma.
• The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment.
• At least one measurable lesion (according to RECIST version 1.1): the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan.
• Patients fail after at least one systemic failure, including surgery, intervention, radiotherapy, chemotherapy and targeted therapy and require palliative treatment.
• Definition of treatment failure: Disease progression during treatment or relapse after treatment, such as after at least once radical or palliative resection surgery, revenue recurrence or progression after intervention therapy or radiotherapy. Intervention therapy or oxaliplatin treatment must be more than 1 cycle, and molecular targeted therapy must more than ≥14 days.
• Definition of intolerance: Grade ≥IV hematologic toxicity, or grade ≥III non- hematologic toxicity, or grade ≥ II damage of heart, liver and kidney during treatment.
• The ECOG score is 0-1 within 1 week before enrollment.
• Liver function assessment: Child-Pugh Grade A or mild Grade B (score ≤ 7), BCLC stage B-C.
• More than 2 weeks from first-line system treatment failure to sign informed consent for this study, and adverse events returned to normal (NCI-CTCAE ≤ I).
• Estimated survival time ≥ 6 months.
• HBV DNA \<2000 IU/ml (10\^4 copies/ml).
• Hematology and organ function are sufficient based on the following laboratory results within 14 days prior to the treatment of this study:
• Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no drugs use): Hb≥100g/L, ANC≥1.5×10\*9/L, PLT≥75×10\*9/L.

You may not qualify if:

• Clinical stage I-III, and/or with any of the following: Suitable for radical surgery; Or, without an assessment lesion after radical surgery; Or, never receive any first line treatment; Or, liver transplantation history or ready for liver transplantation.
• Already known to be allergic to recombinant humanized PD-1 monoclonal antibody drugs and components; known to be allergic to axitinib and components.
• ECOG score ≥ 2 points.
• Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection.
• Received any systemic anti-tumor treatment within 3 months prior to participation in the study, including but not limited to intravenous infused and/or oral chemotherapy, targeted drugs, antibody drugs, and traditional Chinese medicines known to have anticancer effects.
• Ascites with clinical symptoms which requires abdominal puncture or drainage therapy, or Child-Pugh score \>2 points.
• With serious systemic diseases such as heart disease and cerebrovascular disease, and the condition is unstable or uncontrollable.
• Already known active central nervous system metastasis and/or cancerous meningitis. Subjects with stable brain metastases after previous treatment may participate as long as no radiologic evidence of progression lasts for at least four weeks prior to this trial and any neurological symptoms have returned to baseline, and no new or enlarged metastatic evidence in brain and no steroids use for at least 7 days prior to trial treatment. Cancer meningitis should be excluded regardless of clinical stability.
• Surgery was performed within 4 weeks prior to the trial and patients must be evaluated after wound healing.
• Hepatic and renal dysfunction evidence: jaundice, ascites, and/or bilirubin ≥ 2 × ULN, and/or alkaline phosphatase ≥ 3 × ULN, and/or ≥ 3 grade (CTC-AE 5.0) proteinuria (\> 3.5g /24 hours), or renal failure requiring blood dialysis or peritoneal dialysis.
• Urine examination shows urinary protein ≥ ++ or 24 hours urine protein \>1.0g.
• Persistent \>2 grade (CTC-AE5.0) infection.
• History of allogeneic tissue transplantation or solid organ transplantation.
• History of active tuberculosis, such as mycobacterium tuberculosis.
• Intolerant of any drug (or any excipient) in this trial.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (26)

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MeSH Terms

Conditions

Liver Neoplasms; Biliary Tract Neoplasms

Interventions

Axitinib; toripalimab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Haitao Haitao, Prof

  Peking Union Medical College Hospital (PUMCH)

  STUDY CHAIR

Central Study Contacts

Xiaobo Yang, MD

CONTACT

010-69156043; jzlin816@126.com

Haitao Haitao, Prof

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients were confirmed with advanced hepatobiliary malignancies by imaging and histological examination and meet with the inclusive criteria, including hepatocellular carcinoma, cholangiocarcinoma, ampullary carcinoma, gallbladder carcinoma, and mixed cancer).

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 8, 2019
• Study Start: May 1, 2020
• Primary Completion: January 1, 2024
• Study Completion: June 30, 2024
• Last Updated: March 29, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)