mFOLFIRINOX Plus Anlotinib and Sintilimab for Advanced Pancreatic Cancer

Phase 1

Recruiting

• Conditions: Locally Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer
• Interventions: Drug: Anlotinib combined with Sintilimab

• Registration Number: NCT06761027
• Lead Sponsor: Fujian Provincial Hospital

Brief Summary

This study is a prospective, single-arm, multicenter, phase Ib/II clinical trial that treats previously untreated patients with locally advanced or metastatic pancreatic cancer using mFOLFIRINOX in combination with anlotinib and sintilimab. The purpose of this trial is to evaluate the efficacy and safety of this treatment regimen and to preliminarily explore the correlation between biomarkers and treatment outcomes.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-12-23
• Study First Submitted: 2024-12-28
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-04
• Last Update Submitted: 2025-01-04
• Study First Posted: 2025-01-07
• Last Update Posted: 2025-01-07
• Primary Completion: 2027-03
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

1. Fully understand this study and voluntarily sign the informed consent form;
2. Age between 18 and 75 years inclusive, with no gender restrictions;
3. Patients with locally advanced or metastatic pancreatic cancer diagnosed by histology or cytology;
4. No prior anti-cancer treatment;
5. Patients must have at least one measurable lesion (according to RECIST 1.1 criteria);
6. ECOG PS score of 0-1;
7. Expected survival of at least 3 months;
8. No severe organic diseases of the heart, lungs, brain, liver, kidneys, or other organs;
9. Women of childbearing age must agree to use contraceptive measures during the treatment period and for 6 months after the end of treatment; negative serum or urine pregnancy test within 7 days before study enrollment, and must be non-lactating, men must agree to use contraceptive measures during the study period and for 6 months after the study ends.

Exclusion Criteria

1. Have already received or are currently receiving additional anti-tumor treatment measures such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, or traditional Chinese medicine treatment;
2. Known allergies to any of the drugs in the study;
3. Symptomatic brain metastases or metastases with symptom control time less than 2 months;
4. A large liver metastasis burden, occupying more than 70% of the liver volume;
5. Patients with obstructive jaundice whose bilirubin cannot be reduced to the expected level after adequate decompression;
6. Presence of any active autoimmune diseases or patients with autoimmune diseases expected to relapse (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes);
7. History of immunodeficiency; patients currently using immunosuppressants, systemic corticosteroid therapy, or any other form of immunosuppressive treatment;
8. Known genetic or acquired bleeding tendencies (such as coagulation disorders) or thrombosis, such as hemophiliacs; currently using or have recently (within 10 days before the start of the study treatment) used full-dose oral or injectable anticoagulants or thrombolytic drugs for therapeutic purposes (preventive use of low-dose aspirin, low molecular weight heparin is allowed);
9. Serious infections (CTC AE greater than grade 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; baseline chest imaging suggests active pulmonary inflammation, presence of symptoms and signs of infection within 2 weeks before the first use of the study drug, or requiring oral or intravenous antibiotic treatment (excluding the use of antibiotics for prevention);
10. History of other malignant tumors within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma;
11. Patients with mental illness; history of abuse of psychotropic drugs, alcoholism, and drug addiction;
12. Pregnant or lactating women;
13. Deemed by the investigator as unsuitable to participate in this trial for other reasons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
mFOLFIRINOX Plus Anlotinib and Sintilimab	Anlotinib combined with Sintilimab	Phase Ib: 6 patients will receive treatment at dose level-0 and their toxicity will be observed. If 2 or fewer patients experience dose-limiting toxicity, the study will proceed to the phase II part using dose level-0 as the treatment dose. If 3 or more patients have dose-limiting toxicity, another 6 patients will be accrued at a lower dose (dose -1). If two or fewer patients have dose-limiting toxicity, then we proceed with the phase II trial at that dose; otherwise, the trial is discontinued. Dose level - 0: anlotinib at a dose of 10mg per administration, once daily, orally administered on days 1-14, every 3 weeks. Dose level -1: anlotinib at a dose of 8mg per administration, once daily, orally administered on days 1-14, every 3 weeks. Phase II: The efficacy and safety of mFOLFIRINOX combined with anlotinib and sintilimab as first-line treatment for locally advanced or metastatic pancreatic cancer will be conducted at the anlotinib safe dose determined in phase Ib.

Primary Outcome Measures

Name	Time	Method
Objective response rate, ORR	Four weeks after the initiation of medication until the day before surgery	The Objective response rate (ORR) was defined as the complete response (CR) rate or the partial response (PR) rate according to RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Disease control rate, DCR	Four weeks after the initiation of medication until the day before surgery	The Disease control rate (DCR) was defined as the complete response (CR) rate or the partial response (PR) rate or stable disease (SD) rate according to RECIST v1.1.
Overall survival, OS	From date of enrollment until the date of death from any cause, assessed up to 60 months	The Overall survival (OS) was defined as the time between receiving treatment and observing death or loss of follow-up for any reason.
Progression free survival, PFS	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months	The Progression free survival (PFS) was defined as the time between the start of treatment and the progression of intrahepatic and/or extrahepatic tumors, or the occurrence of death or loss of follow-up for any reason.
Toxicity Adverse events	From the initiation of medication, with recordings made whenever an adverse reaction occurs, assessed up to 60 months	Grade 1-5 AEs according to NCI-CTCAE V5.0.

Trial Locations

Locations (4)

First Affiliated Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

Fujian Provincial Hospital; 🇨🇳 Fuzhou, Fujian, China

Mengchao Hepatobiliary Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

Zhangzhou Affiliated Hospital of Fujian Medical University; 🇨🇳 Zhangzhou, Fujian, China