Anlotinib Plus Benmelstobart and AG in First-line Treatment of Advanced Metastatic Pancreatic Cancer (ALTER-PA-001)

NCT06621095 | Not Yet Recruiting Phase 2

• 1 other identifier: LY2024-195-B
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to explore the efficacy and safety of anlotinib combined with benmelstobart and AG (nab-paclitaxel and gemcitabine) as first-line treatment compared with AG (nab-paclitaxel and gemcitabine) in metastatic pancreatic cancer.

Conditions

Pancreatic Cancer; First-line; Metastatic Pancreatic Cancer

Keywords

Metastatic Pancreatic Cancer; First-line; Immunotherapy; Angiogenesis inhibitors; Anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The proportion of patients with complete response or partial response, using RESIST v1.1

  Up to 24 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Duration of Response (DoR)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Safety and tolerability by incidence, severity and outcome of adverse events

  Until 30 day safety follow-up visit

Study Arms (2)

anlotinib + benmelstobart + nab-paclitaxel + gemcitabine

EXPERIMENTAL

Initial treatment: anlotinib + benmelstobart + nab-paclitaxel + gemcitabine. Maintenance treatment (after 8 cycles): anlotinib + benmelstobart + gemcitabine.

Drug: anlotinib + benmelstobart + nab-paclitaxel + gemcitabine

nab-paclitaxel + gemcitabine

ACTIVE COMPARATOR

Initial treatment: nab-paclitaxel + gemcitabine. Maintenance treatment (after 8 cycles): gemcitabine.

Drug: nab-paclitaxel + gemcitabine

Interventions

anlotinib + benmelstobart + nab-paclitaxel + gemcitabine DRUG

1. Before 8 cycles, anlotinib 8mg, po.qd, d1-14; benmelstobart: 1200mg, I.V., D1, Q3W; nab-paclitaxel: 125mg/m2, I.V., D1, D8, Q3W; gemcitabine: 1000/m2, ivgtt for more than 30min, D1, D8, Q3W. The above schemes are repeated every three weeks. 2. After 8 cycles, the regimen is changed to anlotinib 8mg, po.qd, d1-14; benmelstobart: 1200mg, I.V., D1, Q3W; gemcitabine: 1000/m2, ivgtt for more than 30min, D1, D8, Q3W. The regimen is repeated every 3 weeks until the disease progresses or unacceptable toxicity.

anlotinib + benmelstobart + nab-paclitaxel + gemcitabine

nab-paclitaxel + gemcitabine DRUG

1. Before 8 cycles, nab-paclitaxel: 125mg/m2, I.V., D1, D8, Q3W; gemcitabine: 1000/m2, ivgtt for more than 30min, D1, D8, Q3W. The above schemes are repeated every three weeks. 2. After 8 cycles, the regimen is changed to gemcitabine: 1000/m2, ivgtt for more than 30min, D1, D8, Q3W. The regimen is repeated every 3 weeks until the disease progresses or unacceptable toxicity.

nab-paclitaxel + gemcitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old (including 18 and 75 years old);
• Histologically or cytologically confirmed diagnosis of metastatic pancreatic cancer;
• At least one measurable lesion according to RECIST v1.1 criteria (any previous radiotherapy-treated lesion that has not progressed cannot be selected as the target lesion);
• Eastern Cooperation Oncology Group (ECOG) performance status of 0-1;
• Life expectancy ≥ 3 months;
• Adequate organ and bone marrow function, meeting the following criteria (within 7 days before enrollment):
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L Platelet count (PLT) ≥ 90 x 10\^9/L Hemoglobin (HB) ≥ 90 g/L
• Biochemistry:
• Without liver metastasis: Serum total bilirubin (TBIL) ≤ 1.5x the upper limit of normal (ULN); with liver metastasis: TBIL ≤ 2.5 x ULN.
• Without liver metastasis: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN; with liver metastasis: ALT and AST ≤ 5 x ULN.
• Serum creatinine ≤ 1.5 x ULN and creatinine clearance rate ≥ 60 mL/min (calculated by the Cockcroft-Gault formula).
• Adequate coagulation function, defined as an international normalized ratio (INR) or a partial thromboplastin time (APTT) ≤ 1.5 x ULN.
• Women of childbearing age need to take effective contraceptive measures.

You may not qualify if:

• Previously received treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or immune checkpoint inhibitors;
• Received other systemic antitumor treatments within 4 weeks prior to enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy, biological immunotherapy, targeted therapy, photodynamic therapy, and traditional Chinese medicine with clear antitumor indications;
• Have other untreated or concurrent malignancies (excluding cervical carcinoma in situ, well-controlled basal cell or squamous cell carcinoma of the skin, or malignancy that has been treated and has shown no signs or evidence of recurrence for more than 3 years, and patients who do not require systemic therapy at the time of signing informed consent);
• Presence of central nervous system (CNS) metastases or brain metastases before enrollment;
• Underwent any surgery (excluding biopsy), invasive treatment or operation without complete healing of surgical incisions within 4 weeks before enrollment (excluding venous catheter placement and puncture drainage);
• Received radiotherapy within 4 weeks before enrollment (allowable if at least 2 weeks have passed since palliative radiotherapy for bone lesions was completed before starting study medication);
• Previously received any organ transplantation;
• Clinically symptomatic ascites, pleural effusion, or pericardial effusion requiring puncture or drainage, or received drainage of effusions within 14 days before the first dose;
• International normalized ratio (INR) \> 1.5 or partial thromboplastin time (APTT) \> 1.5 x ULN;
• Clinically significant electrolyte abnormalities as determined by the investigator;
• Presence of active gastrointestinal diseases like active gastric and duodenal ulcers, ulcerative colitis, or unremoved tumors with active bleeding, or other conditions judged by the investigator to possibly cause gastrointestinal bleeding or perforation;
• Evidence or history of significant bleeding tendency or episodes within 3 months before enrollment (bleeding \>30 mL, hematemesis, melena, or hematochezia), hemoptysis (\> 5 mL of fresh blood within 4 weeks), or thromboembolic events such as stroke and/or transient ischemic attack within 12 months;
• Any severe and/or uncontrollable disease, including:
• History or presence of interstitial lung disease, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, severely impaired lung function, or other conditions that may interfere with the detection and management of suspected drug-related pulmonary toxicity.
• Clinically significant history of liver diseases, including active hepatitis (Hepatitis B reference: HBsAg positive with HBV DNA \> 1 x 10\^4 copies/mL or \> 2000 IU/mL; Hepatitis C reference: HCV antibody positive with HCV RNA \> 1 x 10\^3 copies/mL), or other hepatitis, clinically significant moderate to severe hepatic cirrhosis; Note: Participants with eligible Hepatitis B or C must receive continuous antiviral treatment to prevent viral reactivation.

Sponsors & Collaborators

• RenJi Hospital: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Renji hospital

Shanghai, Shanghai Municipality, 200127, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

anlotinib; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Liwei Wang, M.D.

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liwei Wang, M.D.

CONTACT

021-58752345; lwwang2013@163.com

Jiujie Cui, M.D.

CONTACT

13621958524; cuijiujie@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of oncology

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 1, 2024
• Study Start: October 30, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)