AG Followed by FOLFIRINOX Both Combined With PD-L1 Antibodies as a Conversion Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

NCT07208539 | Not Yet Recruiting Phase 2

• 1 other identifier: ZSPAC-14
• Study Type: interventional
• Target: 77
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this interventional study is to learn about the clinical efficacy of sequential therapy (albumin paclitaxel, gemcitabine combined with PD-L1 antibodies, followed by liposomal irinotecan, oxaliplatin and 5-FU/LV combined with PD-L1 antibodies). The main questions it aims to answer are: Does the sequential therapy increase the resection rate of borderline resectable / locally advanced pancreatic cancer? Does the sequential therapy represent an effective and safe treatment? Participants will receive two distinct chemotherapy regimens, each combined with a PD-L1 antibody, administered in sequence for two cycles each.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 18-month overall survival (OS) rate

  To test whether the 18-month OS rate of patients with borderline resectable or locally advanced pancreatic cancer treated with the sequential therapy was comparable to that of the historical data of the general adult population.

  From the date of first enrollment to 18 months later.

Secondary Outcomes (7)

• Surgical conversion rate

  From the date of first enrollment to the date of completion of follow-up of the last patient, up to 30 months.

• Overall survival rate (OS)

  From the date of first enrollment to the date of completion of follow-up of the last patient, up to 30 months.

• Event-free survival (EFS)

  From the date of first enrollment to the date of completion of follow-up of the last patient, up to 30 months.

• R0 resection rate

  From the date of first enrollment to the date of completion of follow-up of the last patient, up to 30 months.

• R1 resection rate

  From the date of first enrollment to the date of completion of follow-up of the last patient, up to 30 months.

Study Arms (1)

Sequential therapy

EXPERIMENTAL

Drug: Treatment: AG & anti-PD-L1 + FOLFIRINOX & anti-PD-L1

Interventions

Treatment: AG & anti-PD-L1 + FOLFIRINOX & anti-PD-L1 DRUG

The cohort A (borderline resectable) and cohort B (locally advanced) both received treatment with gemcitabine, albumin paclitaxel (administered on days 1, 8, and 15, with 4 weeks as one cycle) and adalimumab (administered once every 4 weeks, with 4 weeks as one cycle). After completing 2 cycles of treatment, they were sequentially given liposomal irinotecan combined with 5-FU/LV, oxaliplatin (administered once every 2 weeks, with 4 weeks as one cycle) and adalimumab (administered once every 4 weeks, with 4 weeks as one cycle). After completing 2 cycles of sequential treatment, surgical evaluation was conducted: for patients who could undergo radical surgical resection, surgery was performed within 2-4 weeks after the end of the conversion treatment stage, and the postoperative treatment plan was selected based on the investigator's judgment; for patients who could not undergo radical surgical resection, subsequent treatment plans could be selected based on the investigator's judgment.

Sequential therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old, gender not restricted
• According to the NCCN Clinical Practice Guidelines for Pancreatic Cancer (2024.V2 version), patients with borderline resectable/locally advanced pancreatic cancer as evaluated by multidisciplinary and imaging assessment, the definition of borderline resectability includes:
• No distant metastasis;
• Arteries: 1. Pancreatic head/neck: The tumor is in contact with the common hepatic artery and does not extend to the abdominal aorta or the hepatic artery bifurcation, and can be safely resected and reconstructed; the tumor is in contact with the superior mesenteric artery ≤ 180°; the tumor contacts variant arteries (such as the accessory right hepatic artery, replacement of the hepatic right artery, replacement of the common hepatic artery or the starting part of the accessory/secondary artery, etc.), but can be safely resected and reconstructed. 2. Pancreatic body/tail: The tumor is in contact with the abdominal aorta ≤ 180°;
• Veins: The tumor is in contact with the superior mesenteric vein or portal vein \> 180°, or contact ≤ 180° combined with irregular venous contour or venous thrombosis, and there are appropriate blood vessels at the proximal and distal ends of the affected area that can be completely resected and reconstructed; the tumor contacts the inferior vena cava;
• Local advanced pancreatic cancer is defined as:
• <!-- -->
• No distant metastasis;
• Arteries: 1. Pancreatic head/neck: The tumor is in contact with the superior mesenteric artery or the celiac trunk artery \> 180°; 2. Pancreatic body/tail: The tumor is in contact with the superior mesenteric artery or the celiac trunk artery \> 180°; the tumor contacts the celiac trunk artery and invades the abdominal aorta;
• Veins: Due to tumor invasion, vein occlusion or involvement of a large area of the superior mesenteric vein and ileal branch, it is impossible to safely reconstruct the portal vein - superior mesenteric vein;
• No previous anti-tumor treatment (including radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy, etc.), investigational drug treatment;
• Must have at least one measurable lesion as the target lesion (according to RECIST v1.1 standard);
• ECOG: 0 - 1
• Expected survival ≥ 3 months;
• Good function of major organs, that is, in accordance with the following standards (within 14 days before randomization, no blood components, cell growth factors were received):

You may not qualify if:

• Pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine carcinoma, pancreatic acinar cell carcinoma, pancreatic blastoma, solid-pseudopapillary tumors patients
• Patients with known central nervous system metastasis
• Severe gastrointestinal dysfunction (with bleeding, obstruction; grade 2 or higher inflammation; grade 1 or higher diarrhea)
• Randomly within the previous 2 weeks, there was third-space effusion (such as large pleural effusion) that could not reach a stable state (after removing the drainage tube, no intervention treatment was required)
• Abdominal effusion with clinical symptoms, requiring puncture and drainage, or patients who had undergone abdominal effusion drainage within 3 months previously (excluding those with only imaging showing a small amount of abdominal effusion and controllable, but without clinical symptoms)
• Currently accompanied by interstitial pneumonia or interstitial lung disease, or having a history of interstitial pneumonia or interstitial lung disease requiring hormone treatment previously, or other possible pulmonary fibrosis, organizing pneumonia (such as obliterative bronchiolitis), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia or in the screening period, chest CT showing active pneumonia or severely impaired lung function subjects; active tuberculosis
• Presence of active autoimmune disease or having a history of autoimmune disease that may recur \[including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism (only subjects with controlled hormone replacement therapy can be enrolled)\], having a skin disease that does not require systemic treatment such as vitiligo, psoriasis, alopecia, receiving insulin treatment for controlled type 1 diabetes or having completely resolved childhood asthma and no need for any intervention after adulthood, eligible for enrollment
• Known peripheral neuropathy (CTCAE ≥ 3 grade)
• Known dihydroorotate dehydrogenase (low activity) or deficiency
• Randomly within the previous 2 weeks, had severe infection (CTCAE \> 2 grade), such as severe pneumonia requiring hospitalization, sepsis, infection complications, etc.; randomly within the previous 2 weeks, had symptoms and signs of infection requiring intravenous antibiotic treatment (except for prophylactic use of antibiotics)
• Had received any of the following treatments:
• Randomly within the previous 2 weeks, the medication used included strong inhibitors/inducers of CYP3A4, CYP2C8 or strong inhibitors of UGT1A1;
• Randomly within the previous 2 weeks, received immunosuppressants or systemic hormone treatment to achieve immunosuppression purposes (dose \> 10mg/day prednisone or other equivalent efficacy hormones);
• Randomly within the previous 2 weeks, received radiotherapy;
• Randomly within the previous 4 weeks, underwent major surgery (such as thoracotomy, laparotomy, etc.);

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Wenquan Wang

CONTACT

+86 21 31587861; wang.wenquan@zs-hospital.sh.cn

Study Design

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

Study Record Dates

• First Submitted: September 28, 2025
• First Posted: October 6, 2025
• Study Start: October 10, 2025
• Primary Completion: April 9, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share