Axitinib Plus Toripalimab as Second-line Treatment in Hepatobiliary Malignant Tumors: a Single-arm, Non-randomized, Single-center Phase II Trial
Overview
- Phase
- Phase 2
- Intervention
- axitinib plus toripalimab
- Conditions
- Hepatobiliary Neoplasm
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
This phase II trial is a single-arm, non-randomized and single-center clinical study. It is estimated that 60 patients who met the study criteria will be enrolled in PUMCH and treated with axitinib plus toripalimab. The investigators will follow up and collect subjects' data each month to evaluate the efficacy and safety of treatment, including overall survival and time to progression, until disease progression or death. Histopathology and multi-omics data analysis will be used to explore potential biomarkers of treatment response. Study Type: Interventional. Masking: Open Label.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following criteria
- •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.
Exclusion Criteria
- •Subjects with one or more than one of the following criteria should be excluded
- •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.
Arms & Interventions
axitinib plus toripalimab
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.
Intervention: axitinib plus toripalimab
Outcomes
Primary Outcomes
objective response rate (ORR)
Time Frame: one year
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.
Progression-free Survival (PFS)
Time Frame: six months
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.
Secondary Outcomes
- Duration of Response (DOR)(one year)
- Disease Control Rate (DCR)(one year)
- Stable Disease (SD)(one year)
- Progression free survival rate(six months)
- Overall Survival (OS)(two years)
- Rate of 6-months and 1-year overall survival(one year)