Lenvatinib Combined Pembrolizumab in Advanced Hepatobiliary Tumors

NCT03895970 | Completed Phase 2

• 1 other identifier: JS-1864
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Liver Neoplasm Malignant Primary; Cholangiocarcinoma; Combinational Immunotherapy; Biomarker

Keywords

Hepatobiliary Cancer; Pembrolizumab; Lenvatinib; Biomarker

Outcome Measures

Primary Outcomes (3)

• 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

• Disease Control Rate (DCR)

  Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.

  one year

• Progression-free Survival (PFS)

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

  six months

Secondary Outcomes (3)

• Overall Survival (OS)

  two years

• Duration of Response (DOR)

  one year

• Stable Disease

  one year

Other Outcomes (1)

• Incidence of Treatment-Emergent Adverse Event

  two year

Study Arms (1)

Lenvatinib plus Pembrolizumab

EXPERIMENTAL

Lenvatinib is a novel angiogenesis inhibitor which targets vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT. Pembrolizumab is a recombinant anti-human PD-1 monoclonal antibody.

Drug: Lenvatinib plus Pembrolizumab

Interventions

Lenvatinib plus Pembrolizumab DRUG

Lenvatinib 12mg, once a day, oral at least 38 days of each 6 weeks cycle. Pembrolizumab 200mg, every 3 weeks, intravenous infused of each 6 weeks cycle. Number of cycle: until progression or unacceptable toxicity develops.

Also known as: Lenvatinib (Lenvima, Eisai China), Pembrolizumab (Keytruda, MSD China)

Lenvatinib plus Pembrolizumab

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 lymphadenpathy 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 0-2 within 1 week before enrollment.
• Liver function assessment: Child-Pugh Grade A or mild Grade B (≤ 7 points), 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 (104 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≥90g/L, ANC≥1.5×10\*9/L, PLT≥80×10\*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.
• ECOG score ≥ 3 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.
• Ascites with clinical symptoms which requires abdominal puncture or drainage therapy, or Child-Pugh score \>2.
• 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 ≥ 1.5 × 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (25)

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MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Haitao Zhao, Prof

  Peking Union Medical College Hospital (PUMCH)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• 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: March 28, 2019
• First Posted: March 29, 2019
• Study Start: April 20, 2019
• Primary Completion: April 1, 2021
• Study Completion: August 1, 2021
• Last Updated: March 29, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)