Gemcitabine Plus Nab-paclitaxel as Switch Maintenance Versus Continuation of Modified FOLFIRINOX as 1st Line Chemotherapy in Patients With Advanced Pancreatic Cancer.

NCT06897644 | Recruiting Phase 3 DMC

• 2 other identifiers: PANThEON2024-515214-41-00
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 28

Brief Summary

PANThEON is a randomized, open-label, multicenter phase III trial aimed at comparing the switch maintenance with gemcitabine plus nab-paclitaxel (ARM B) versus mFOLFIRINOX continuation (ARM A) in terms of overall survival (OS) in patients with unresectable LAD or mPDAC without disease progression following 3 months of induction mFOLFIRINOX triplet chemotherapy.

Conditions

Pancreatic Adenocarcinoma Advanced or Metastatic

Keywords

first line; mFOLFIRINOX; chemotherapy; pancreas; Gemcitabine with Nab-Paclitaxel; switch maintenance; pancreatic cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  OS is defined as the time from randomization to the date of death due to any cause. For patients still alive at the time of analysis, the OS time will be censored on the last date the patients were known to be alive.

  from date of randomization to date of death (or last follow up for alive patients), assessed up to 48 months

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  from randomization to disease progression or death from any cause, assessed up to 48 months

• Time to Treatment Failure (TTF)

  from randomization to discontinuation of treatment for any reason, including progressive disease, treatment toxicity and death, assessed up to 48 months

• Objective Response Rate (ORR)

  up to 48 months

• Disease Control Rate (DCR)

  Up to approximately 48 months

• Quality of life (QoL)

  Up to approximately 48 months

Study Arms (2)

ARM A - continuation of mFOLFIRINOX

ACTIVE COMPARATOR

Patients in Arm A will receive continuation of the same regimen used as induction chemotherapy: * Oxaliplatin 85 mg/sqm; * Irinotecan 150 mg/sqm; * Leucovorin 400 mg/sqm (racemic) or l-Leucovorin 200 mg/sqm; * 5-FU 2400 mg/sqm 46-hours infusion; every 2 weeks. Treatment will continue until PD, unacceptable toxicity, informed consent withdrawal, or patient's death. In case of permanent discontinuation of one or more compounds due to unacceptable toxicity, treatment with the other agent(s) may be continued until PD.

Drug: Oxaliplatin; Drug: Irinotecan (CPT-11); Drug: Leucovorin; Drug: 5-FU (5-fluorouracil)

ARM B - switch maintenance with Gem-NabP

EXPERIMENTAL

Patients in Arm B will receive: * Gemcitabine 1000 mg/sqm on Days 1,8,15 of every 28-day cycles; * Nab-Paclitaxel 125 mg/sqm on Days 1,8,15 of every 28-day cycles. Treatment will continue until PD, unacceptable toxicity, informed consent withdrawal, or patient's death. In case of permanent discontinuation of one compound due to unacceptable toxicity, treatment with the other agent may be continued until PD in each arm.

Drug: gemcitabine; Drug: Nab-paclitaxel

Interventions

Oxaliplatin DRUG

85 mg/sqm iv over 2 hours day 1

ARM A - continuation of mFOLFIRINOX

Irinotecan (CPT-11) DRUG

150 mg/sqm iv over 60 minutes day 1

ARM A - continuation of mFOLFIRINOX

Leucovorin DRUG

Leucovorin 400 mg/sqm (racemic) or l-Leucovorin 200 mg/sqm over 2 hours day 1

ARM A - continuation of mFOLFIRINOX

5-FU (5-fluorouracil) DRUG

2400 mg/sqm 46-hours infusion

ARM A - continuation of mFOLFIRINOX

gemcitabine DRUG

1000 mg/sqm over 30 minutes on Days 1,8,15 of a 28-day cycles

ARM B - switch maintenance with Gem-NabP

Nab-paclitaxel DRUG

125 mg/sqm over 30 minutes on Days 1,8,15 of a 28-day cycles

ARM B - switch maintenance with Gem-NabP

Eligibility Criteria

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

You may qualify if:

• Patient able and willing to provide written informed consent and to comply with the study protocol.
• Subjects must be ≥18 years.
• Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma eligible for treatment in the first-line setting.
• Presence of measurable or non-measurable disease assessed by CT scan and/or MRI according to RECIST 1.1. Note: any lesion which has been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure.
• Availability of archival tumor sample (primary tumor or metastatic site) for biomarker analysis.
• ECOG performance status of 0-1 (if age \< 70 years). If age ≥70 years, ECOG PS must be 0.
• Estimated life expectancy \> 3 months.
• Adequate baseline hematologic function characterized by the following at screening:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L.
• Platelets count ≥ 100 × 109/L.
• Hemoglobin ≥ 9 g/dl. Note: prior transfusions for patients with low hemoglobin are allowed.
• Adequate liver function characterized by the following at screening:
• Serum total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or \< 40% of total bilirubin are allowed.
• Serum transaminases (AST and/or ALT) \< 3 x ULN (\< 5 x ULN in presence of liver metastasis). In participants with elevated AST or ALT, the values must be stable for at least 2 week and with no evidence of biliary obstruction by imaging.
• Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min.

You may not qualify if:

• Pancreatic neuroendocrine, acinar, squamous/adenosquamous, or islet tumors.
• Previous or concurrent systemic (e.g. cytotoxic or targeted or other experimental drugs) therapy for advanced pancreatic adenocarcinoma.
• Note: previous (neo)adjuvant or perioperative anti-cancer therapy for non-metastatic, resectable or borderline resectable PDAC, associated with surgery on the primary tumor, is allowed if \> 9 months have elapsed from the last dose of therapy and documented disease progression or relapse.
• Major surgery or radiation therapy performed within \<4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if performed \> 2 weeks prior to start of study treatment. Patients must have recovered from an effect from major surgery.
• Known allergy or hypersensitivity to study drugs and/or their excipients.
• Unresolved toxicity ≥ CTCAE grade 2 attributed to any prior therapies (e.g. grade ≥2 peripheral neurotoxicity), excluding anemia or alopecia.
• Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that requires directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study entry.
• Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years prior to study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer.
• Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible.
• Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment.
• Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and patients must be compliant with antiretroviral treatment.
• Pregnant or breast-feeding patient, or patient planning to become pregnant within 7 months after the end of treatment.
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA \> II, unstable angina pectoris, history of myocardial infarction within 3 months before study entry, significant arrhythmia).
• Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent.
• Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial.

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead
• Rising Tide Foundation: collaborator

Study Sites (28)

Centro Di Riferimento Oncologico Di Aviano

Aviano, Italy, 33081, Italy

RECRUITING

University Hospital Consorziale Policlinico

Bari, Italy, 70124, Italy

NOT YET RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, Italy, 25123, Italy

NOT YET RECRUITING

ASST Ospedale Maggiore di Crema

Crema, Italy, 26013, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Di Cremona

Cremona, Italy, 26100, Italy

NOT YET RECRUITING

Careggi University Hospital

Florence, Italy, 50134, Italy

NOT YET RECRUITING

IRCCS Ospedale Policlinico San Martino

Genoa, Italy, 16132, Italy

NOT YET RECRUITING

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Meldola, Italy, 47014, Italy

RECRUITING

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, Italy, 20122, Italy

NOT YET RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, 20133, Italy

NOT YET RECRUITING

Istituto Europeo Di Oncologia S.r.l.

Milan, Italy, 20141, Italy

NOT YET RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy, 20162, Italy

RECRUITING

Humanitas Istituto Clinico Catanese S.p.A.

Misterbianco, Italy, 95045, Italy

NOT YET RECRUITING

Azienda Sanitaria Locale Napoli 1 Centro

Napoli, Italy, 80147, Italy

NOT YET RECRUITING

Azienda Ospedaliero-Universitaria Maggiore Della Carità

Novara, Italy, 28100, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, Italy, 35128, Italy

RECRUITING

Azienda Ospedaliero Universitaria Parma

Parma, Italy, 43126, Italy

NOT YET RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy, 27100, Italy

NOT YET RECRUITING

Azienda Sanitaria Territoriale Di Pesaro E Urbino

Pesaro, Italy, 61122, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy, 56126, Italy

RECRUITING

Azienda Sanitaria Locale Della Provincia Di Biella

Ponderano, Italy, 13875, Italy

RECRUITING

Azienda USL Toscana Centro

Prato, Italy, 59100, Italy

RECRUITING

Azienda Unita Sanitaria Locale Della Romagna

Ravenna, Italy, 48121, Italy

RECRUITING

I.F.O. Istituti Fisioterapici Ospitalieri

Rome, Italy, 00144, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Italy, 00168, Italy

NOT YET RECRUITING

Humanitas Mirasole S.p.A.

Rozzano, Italy, 20089, Italy

NOT YET RECRUITING

Pia Fondazione Di Culto E Religione Cardinale Giovanni Panico

Tricase, Italy, 73039, Italy

NOT YET RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Italy, 33100, Italy

NOT YET RECRUITING

Related Publications (1)

• Sciortino C, Nichetti F, Bergamo F, Palermo F, Tamberi S, Vivaldi C, Ongaro E, Arcangeli G, Marchesi S, Giommoni E, Cella CA, Pircher C, Chiaramonte A, Bencardino K, Sottotetti E, Martinetti A, Rapposelli IG, Corallo S, Di Donato S, Murialdo R, Delliponti L, Salvatore L, Bozzarelli S, Dell'Aquila E, Miceli R, Carnaghi C, Tomasello G, Rivizzigno P, Bonomi M, Mannavola F, Forti L, Garajova I, Attademo L, Galassi B, Chiari R, Leone F, Garattini SK, Tamburini E, Pietrantonio F, Niger M. A phase III randomized clinical trial of Gemcitabine and Nab-Paclitaxel as switch maintenance versus continuation of modified FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: The PANThEON Study. Dig Liver Dis. 2025 Dec;57(12):2470-2477. doi: 10.1016/j.dld.2025.11.007. Epub 2025 Nov 28.

  PMID: 41318310 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Monica Niger, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monica Niger, MD

CONTACT

+3902 2390 2919; monica.niger@istitutotumori.mi.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: March 27, 2025
• Study Start: March 27, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (28)