Durvalumab and Lenvatinib With or Without Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer

NCT05935579 | Unknown Phase 2

• 1 other identifier: K3112
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Explore the impact of the first-line application of Durvalumab combined with Lenvatinib, with or without chemotherapy, on the survival, disease progression, and drug safety of patients with advanced biliary tract cancers.

Conditions

Biliary Tract Neoplasms; Immunotherapy

Keywords

Biliary Tract Neoplasms; Durvalumab; Lenvatinib; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The proportion of patients whose tumor volume shrinks to a predetermined value and can maintain the minimum required duration, including complete response and partial response.

  Baseline up to approximately 6 months

Secondary Outcomes (7)

• Disease control rate

  Baseline up to approximately 6 months

• Progression-free survival

  Baseline up to approximately 12 months

• Overall survival

  Baseline up to approximately 12 months

• Duration of response

  Baseline up to approximately 12 months

• Clinical benefit rate

  Baseline up to approximately 12 months

Study Arms (2)

Durvalumab and Lenvatinib

EXPERIMENTAL

Drug: Durvalumab; Drug: Lenvatinib Oral Product

Durvalumab and Lenvatinib plus chemotherapy

ACTIVE COMPARATOR

Drug: Durvalumab; Drug: Lenvatinib Oral Product; Drug: Chemotherapy

Interventions

Durvalumab DRUG

Durvalumab 1500 mg will be administered intravenously once every three weeks, with intravenous infusion on Day 1 of each cycle.

Durvalumab and Lenvatinib; Durvalumab and Lenvatinib plus chemotherapy

Lenvatinib Oral Product DRUG

The dose of lenvatinib is 12mg/day for patients with a body weight of ≥60 kg, and 8mg/day for patients with a body weight of \<60 kg, taken once daily.

Durvalumab and Lenvatinib; Durvalumab and Lenvatinib plus chemotherapy

Chemotherapy DRUG

GEMOX regimen: Gemcitabine 1000mg/m2 will be administered intravenously over 30 minutes on Day 1 and Day 8; Oxaliplatin 100mg/m2 will be administered intravenously over 2 hours on Day 1, and the cycle will be repeated every 3 weeks.

Durvalumab and Lenvatinib plus chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily participate in the study and agree to sign the informed consent form, are compliant, and cooperate with follow-up.
• They are over 18 years of age and gender is not restricted when signing the informed consent form.
• They have histologically confirmed unresectable advanced or metastatic biliary tract adenocarcinoma, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder cancer.
• They have at least one measurable lesion (as defined by RECIST 1.1, the measurable lesion is a spiral CT scan long diameter ≥10mm or lymph node short diameter ≥15mm).
• Their ECOG score is 0-1 in the week prior to enrollment.
• Based on the investigator's assessment, their estimated survival time is ≥3 months.
• Patients with active hepatitis B or C require relevant antiviral treatment, with HBV-DNA \<2000 IU/ml (\<104 copies/ml), and have received at least 14 days of antiviral treatment before participating in the study. HCV RNA-positive patients must follow local standard treatment guidelines for antiviral therapy, and their liver function is within CTCAE Grade 1 elevation.
• Their hematological and organ functions are adequate, based on laboratory test results obtained within 14 days before the start of the study (unless otherwise specified):
• Hematology: (no blood transfusion, no G-CSF, no drug correction within 14 days prior to screening) Hb ≥90 g/L; neutrophil count ≥1.5×109/L; PLT ≥100×109/L.
• Biochemistry: (no albumin transfusion within 14 days) Appropriate liver function: ALT and AST ≤2.5×ULN; for patients with liver metastases, ALT and AST ≤5 × ULN.
• Serum bilirubin ≤2.0×ULN; these conditions do not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization.
• Appropriate renal function: creatinine ≤1.5×ULN, or creatinine clearance rate (CCr) \>50mL/min (using the standard Cockcroft-Gault formula):
• Female: CrCl = ((140 - age) x weight (kg) x 0.85) / 72 x serum creatinine (mg/dL) Male: CrCl = ((140 - age) x weight (kg) x 1.00) / 72 x serum creatinine (mg/dL)
• ●Women of childbearing potential: agree to abstain from sexual intercourse or use contraceptive methods with a failure rate of less than 1% during the treatment period and for at least 6 months after the last dose.
• If a female patient has menstruation and has not reached menopause (continuous absence of menstruation for ≥12 months without other reasons), and has not undergone sterilization surgery (removal of ovaries and/or uterus), she is considered to be of childbearing potential.

You may not qualify if:

• Previous systemic treatment received.
• ECOG score \> 1.
• Pancreatic cancer.
• Pregnant (positive pregnancy test before medication) or breastfeeding women.
• Known allergy or intolerance to recombinant humanized PD-1 monoclonal antibody drugs, lenvatinib and its components (or any excipients).
• Received local anti-tumor treatment within 4 weeks before the first study drug treatment, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection (allowing palliative radiotherapy for bone metastases at least 2 weeks before study drug treatment).
• Previous or existing grade 3 or higher gastrointestinal fistula or non-gastrointestinal fistula (such as skin) according to CTCAE 5.0 criteria.
• Multiple factors affecting oral administration of lenvatinib (such as inability to swallow, chronic diarrhea and intestinal obstruction, or other conditions that significantly affect drug intake and absorption).
• Major surgery (except biopsy) has been performed within 4 weeks before the first study drug treatment, or the surgical incision has not completely healed; minor surgery (such as simple excision, biopsy, etc.) was performed within 7 days before the first study intervention.
• Significant cardiovascular and cerebrovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accidents or transient ischemic attacks within 6 months before enrollment, congestive heart failure (New York Heart Association classification ≥2), arrhythmia requiring antiarrhythmic drugs (except beta blockers or digoxin), and repeated electrocardiogram showing QTc interval \>480 milliseconds (ms).
• Hepatic or renal dysfunction, with manifestations such as jaundice, ascites, and/or bilirubin \>3×ULN, creatinine ratio \>3.5g/24 hours, or renal failure requiring blood or peritoneal dialysis, and/or urinary routine showing urine protein ≥++ or confirmed 24-hour urine protein quantification \>1.0g.
• Persistent infection \> grade 2 (CTCAE 5.0).
• History of thrombotic events (including stroke and/or transient ischemic attacks) within the past 6 months.
• Poorly controlled hypertension (systolic blood pressure \>160mmHg, diastolic blood pressure \>100mmHg) despite treatment with antihypertensive medications.
• Active autoimmune disease or history of autoimmune disease within the past 2 years; participants with active, known, or suspected autoimmune diseases that may affect important organ function or require systemic immunosuppressive therapy are excluded, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome associated with thrombosis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. However, participants with type 1 diabetes, hypothyroidism requiring only hormone replacement, skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, or alopecia) or participants who will not relapse without external triggering factors are allowed. Replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital (CAMS&PUMCH)

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

durvalumab; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

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

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 7, 2023
• Study Start: December 14, 2022
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: November 15, 2023

Record last verified: 2023-11

Locations

CN (1)