Neoadjuvant Treatment vs Upfront Surgery for Left-Sided Pancreatic Cancer

NCT07155629 | Not Yet Recruiting Phase 3

• 1 other identifier: HUS-LeftPanc-2025
• Study Type: interventional
• Target: 381
• Locations: 1 country
• Sites: 2

Brief Summary

Pancreatic cancer is one of the most treatment resistant malignancies, often diagnosed at a late stage and associated with poor survival. The 5-year overall survival rate remains around 10%. Prognosis is affected by multiple factors including tumor stage, biology, treatment response, and anatomical location. Distal (left-sided) pancreatic cancer, originating from the body or tail of the pancreas, accounts for approximately 20-25% of all pancreatic cancers and has been associated with worse survival than pancreatic head cancer, even when adjusted for stage. This may be due to histological, molecular, and embryological differences, and varied systemic therapy responses. Neoadjuvant chemotherapy has become increasingly important in managing pancreatic cancer. It may improve outcomes by reducing tumor size, allowing for more complete (R0) resections, treating micrometastatic disease early, and identifying patients unlikely to benefit from surgery. While neoadjuvant therapy is recommended for borderline resectable and locally advanced tumors, randomized trials have not shown benefit for patients with upfront resectable pancreatic head cancer. Importantly, no randomized controlled trials have investigated the benefit of neoadjuvant treatment specifically in patients with upfront resectable left-sided pancreatic cancer, despite its distinct biology and worse prognosis. Retrospective data suggest neoadjuvant therapy may improve survival in left-sided tumors. A recent multicenter study reported significantly longer overall survival in patients treated with neoadjuvant therapy compared to upfront surgery alone. However, prospective randomized data are lacking. This multicenter randomized trial aims to assess whether patients with resectable left-sided pancreatic cancer benefit from neoadjuvant chemotherapy compared to upfront surgery. The study will reflect real-world clinical practice by allowing both commonly used regimens-FOLFIRINOX and Gemcitaine-Nab-paclitaxel -as neoadjuvant options. Previous studies have shown these regimens to be similarly effective, and switching between them due to toxicity or progression is feasible and does not seem to impair surgical outcomes or survival. This study aims to evaluate the benefits of neoadjuvant chemotherapy before surgery in a prospective multicenter randomized setting for resectable left-sided pancreatic cancer patients.

Conditions

Pancreatic Cancer Resectable

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival of participants, defined as the time from randomization until death from any cause, analyzed in the intention-to-treat (ITT) population.

  From randomization until death or study completion, up to approximately 5 years.

Study Arms (2)

Perioperative chemotherapy

EXPERIMENTAL

Patients who undergo surgical resection will receive adjuvant chemotherapy with 4 cycles (2 months) of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and 5-fluorouracil (400 mg/m2 bolus then 2400 mg/m2 over 46 h)) OR 2 cycles (2 months) of Gemcitabine 1000 mg/m2 over 30 min at day 1, 8, 15 of each 28-day cycle and capecitabine 830 mg/m2 ×2 daily for 3 weeks and one week rest of each 28-day cycle. Regimen changes due to toxicity are allowed. After 2 and 4 months of NAT, response imaging (multiphased body CT) is assessed at a local pancreatic MDT. If stable disease or regression is observed, patients will undergo surgery after chemotherapy break of 3-6 weeks. Adjuvant chemotherapy (2-4 months) must be started within 4-12 weeks after resection. Dose adjustments follow local practice; adjuvant therapy depends on patient condition (mFOLFIRINOX, Gem+capecitabine, or gemcitabine alone).

Drug: mFOLFIRINOX neoadjuvant chemotherapy / Nab-paclitaxel and gemcitabine

Control arm

NO INTERVENTION

After randomization, arm B patients are scheduled for upfront surgery. Adjuvant chemotherapy of 6 months must be started within 4-12 weeks after resection. Dose reduction or dose delays are acted upon according to local clinical practice at each centre. The adjuvant therapy is decided and if necessary modified according to patient's condition (mFOLFIRINOX, Gem+cabecitabine, single Gem).

Interventions

mFOLFIRINOX neoadjuvant chemotherapy / Nab-paclitaxel and gemcitabine DRUG

The benefits of neoadjuvant chemotherapy before surgery in a prospective multicenter randomized setting for resectable left-sided pancreatic cancer patients.

Also known as: oxaliplatin, irinotecan, leucovorin, 5-fluorouracil, gemcitabine, Nanoparticle albumin bound paclitaxel

Perioperative chemotherapy

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Resectable left pancreatic cancer according to NCCN criteria
• Written and informed consent
• Age \> 18y
• ECOG 0-2
• Fit for surgery
• Fit for neoadjuvant chemotherapy

You may not qualify if:

• ECOG \> 2
• Histology other than ductal adenocarcinoma
• Unable to give written consent
• \< 18y

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Oulu University Hospital: collaborator

Study Sites (2)

Helsinki University Central Hospital

Helsinki, 00290, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

MeSH Terms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Taxes

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Economics; Health Care Economics and Organizations

Study Officials

• Hanna Seppänen, Adj. Prof., Pancreatic surgeon

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hanna Seppänen, Adj. Prof., Pancreatic surgeon

CONTACT

+358-50-4270042; hanna.seppanen@hus.fi

Mari Ainola, Adj. prof.

CONTACT

+358-50-5306400; mari.ainola@hus.fi

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Adjunct Professor, Pancreatic surgeon

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 4, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): August 31, 2030
• Last Updated: September 4, 2025

Record last verified: 2025-09

Locations

FI (2)