Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers

NCT04211168 | Unknown Phase 2 DMC

• 1 other identifier: JS-2171
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators design a phase II clinical study to explore the efficacy and safety of toripalimab plus lenvatinib as a second-line treatment in patients with advanced biliary tract cancers and to analyze potential biomarkers of therapeutic response.

Conditions

Advanced Biliary Tract Cancer

Keywords

Intrahepatic cholangiocarcinoma; hilar cholangiocarcinoma; common bile duct cancer; gallbladder cancer; Toripalimab; Lenvatinib; 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.

  two years

• Rate of adverse events (AE)

  the incidence rate of any adverse events related with treatment drugs and details include adverse events type, frequency and severity.

  two years

Secondary Outcomes (6)

• Overall Survival (OS)

  two years

• Progression-free Survival (PFS)

  six months

• Stable Disease (SD)

  two years

• Clinical benefit rate (CBR)

  two years

• Progression free survival rate

  6 months

Other Outcomes (1)

• Biomarkers

  two years

Study Arms (1)

Toripalimab Plus Lenvatinib

EXPERIMENTAL

Toripalimab (Shanghai Junshi Biosciences Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.

Drug: Toripalimab plus Lenvatinib

Interventions

Toripalimab plus Lenvatinib DRUG

Toripalimab 240mg, every 3 weeks, intravenous infused, day 1, 6 weeks a cycle. Lenvatinib 8mg (weight\<60kg) or 12mg (weight≥60kg), once a day, orally, day 2, 6 weeks a cycle. Dose reduction to 4mg/d or dose termination is allowed according to adverse events. Number of cycle: until progression or unacceptable toxicity events develop.

Also known as: JS001 plus E7080

Toripalimab Plus Lenvatinib

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 biliary tract cancers by imaging and histological examination, including intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, common bile duct cancer and gallbladder cancer. Advanced biliary tract cancers refer to unresectable, recurrent, locally advanced and metastatic lesions which are defined as stage IIIA or above according to the 8th AJCC stage system.
• The disease is not suitable for radical surgery and/or topical treatment, or disease progression occurs after surgery and/or local treatment, including lesion resection, ablation, transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), radiotherapy at least 4 weeks before the baseline assessment. All acute toxic effects of local treatment must be ≤ CTCAE 5.0 Level 1.
• Patients are intolerant or fail after first-line systemic treatment (gemcitabine or platinum based regimen) and require palliative treatment. The first-line system treatment failure was ≥ 1 month before enrollment in this study (signing informed consent) and adverse events are controlled (NCI-CTCAE ≤ Grade Ⅰ). i) Definition of systemic treatment: Gemcitabine or platinum based regimen for more than 1 cycle. Adjuvant chemotherapy based on gemcitabine or platinum is considered as first-line treatment if recurrence occur during or after 6 months adjuvant chemotherapy sequential to tumor resection. ii) Definition of treatment failure: Disease progression occur during treatment or in 6 months after the last cycle. iii) Definition of intolerance: Grade ≥IV hematologic toxicity; grade ≥III toxicity of liver, kidney and skin; grade ≥ II toxicity of heart, lung and brain.
• Prior treatment must not include lenvatinib, PD-1 / PD-L1 antibodies or molecular targeted therapy for ≥ 14 days.
• 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.
• Blood pressure is controlled \<= 150/90 mmHg with no more than 3 antihypertensive drugs.
• The ECOG score is 0-1 within 1 week before enrollment.
• Estimated survival time ≥ 12 weeks.
• Liver function assessment: Child-Pugh Grade A or mild Grade B (score ≤ 7).Only one of albumin and bilirubin is Child-Pugh score 2.
• Patients with active hepatitis B and C need to receive relevant antiviral treatment. HBV DNA \<2000 IU/ml (10\^4 copies/ml) and HCV-RNA negative.
• No more than 2 organs metastasis, including liver, lung, bone and brain.
• Hematology and organ function are well based on the following laboratory results within 14 days prior to the treatment of this study: i) 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. ii) Biochemical examination (no ALB infused within 14 days): ALB≥30g/L, ALT, AST and ALP\<5×ULN, TBIL≤60 μmol/L, creatinine≤1.5×ULN or CCr \>50mL/min. iii) Coagulation function: International standardized ratio (INR) ≤ 1.5 × upper limit of normal (ULN), or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; or PT ≤ULN + 4s.
• No active autoimmune diseases that require systemic therapy in the past 2 years (note: active state means requiring disease modulators, corticosteroids or immunosuppressive drugs use). Alternative therapies, such as thyroxine, insulin or a physiological corticosteroid replacement therapy are not considered as systemic therapy.

You may not qualify if:

• Patients meet with any of the following condition: Suitable for radical surgery; Or, without an assessment lesion after radical surgery; Or, never receive any first line treatment.
• Patients who received first-line chemotherapy within 1 month when participating in the study.
• Already known to be allergic or intolerant to recombinant humanized PD-1 monoclonal antibody drugs (or components) or lenvatinib.
• Previously received with lenvatinib, or any anti-vascular endothelial growth factor (VEGF) or VEGF receptor targeted drug, or any anti-PD-1, anti-PD-L1 or anti-PD-L2 or CTLA-4 drug, including antibodies involved in JS001 clinical studies.
• ECOG score ≥ 2 points.
• Hepatic encephalopathy.
• Histopathological result show mixed liver cancer, squamous cell carcinoma or sarcoma cell component.
• More than 2 organs metastasis, including liver, lung, bone and brain.
• pregnant women (positive pregnancy test before taking the drug) or lactating women.
• Patients with bone metastases who had received palliative radiotherapy within 4 weeks before participating in the study (radiotherapy area\>5% bone marrow area).
• 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.
• Patients are receiving approved or developing systemic anti-cancer therapies, including chemotherapy, bio-immunotherapy, targeted therapy, or traditional Chinese medicine therapy with clear indications. Treatment received 4 weeks before randomization is permitted.
• Tumors or liver metastasis occupied more than 50% of liver volume.
• Portal vein trunk (Vp4) or inferior cavity or atrium is affected by tumor thrombus.

Sponsors & Collaborators

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

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

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MeSH Terms

Conditions

Cholangiocarcinoma; Klatskin Tumor; Gallbladder Neoplasms

Interventions

toripalimab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases

Study Officials

• Haitao Zhao, MD

  Peking Union Medical College Hospital (PUMCH)

  STUDY CHAIR

Central Study Contacts

Xiaobo Yang, MD

CONTACT

010-69156043; yangxulcyx@163.com

Haitao Zhao, MD

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 are confirmed with advanced biliary tract cancers by imaging and histological examination and meet with the inclusive criteria, including intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, common bile duct cancer and gallbladder cancer.

Study Record Dates

• First Submitted: December 22, 2019
• First Posted: December 26, 2019
• Study Start: August 11, 2020
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 29, 2023

Record last verified: 2022-10

Locations

CN (1)