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

NCT ID: NCT06897644

Last Updated: 2025-05-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-03-27

Study Completion Date

2030-01-01

Brief Summary

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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.

Detailed Description

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

The induction chemotherapy regimen will be mFOLFIRINOX as per standard of care. Treatment must be continued for up to a maximum of 14 weeks, corresponding to \~ 6 bi-weekly cycles. A minimum of 4 treatment cycles administered is necessary for the patient to be evaluable for randomization.

Radiological tumor assessment will be performed before the start and after completion of induction chemotherapy. Patients with complete/partial response or stable disease (CR/PR/SD) or without evidence of progressive disease (PD) in case of non-measurable disease will be randomized in a 1:1 ratio.

Stratification factors will be ECOG Performance status (PS, 0 vs 1) and disease extension (LAD vs metastatic with presence of liver metastases vs metastatic without presence of liver metastases).

Conditions

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Pancreatic Adenocarcinoma Advanced or Metastatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ARM A - continuation of mFOLFIRINOX

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.

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

85 mg/sqm iv over 2 hours day 1

Irinotecan (CPT-11)

Intervention Type DRUG

150 mg/sqm iv over 60 minutes day 1

Leucovorin

Intervention Type DRUG

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

5-FU (5-fluorouracil)

Intervention Type DRUG

2400 mg/sqm 46-hours infusion

ARM B - switch maintenance with Gem-NabP

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.

Group Type EXPERIMENTAL

gemcitabine

Intervention Type DRUG

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

Nab-paclitaxel

Intervention Type DRUG

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

Interventions

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Oxaliplatin

85 mg/sqm iv over 2 hours day 1

Intervention Type DRUG

Irinotecan (CPT-11)

150 mg/sqm iv over 60 minutes day 1

Intervention Type DRUG

Leucovorin

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

Intervention Type DRUG

5-FU (5-fluorouracil)

2400 mg/sqm 46-hours infusion

Intervention Type DRUG

gemcitabine

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

Intervention Type DRUG

Nab-paclitaxel

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.
* Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
* No presence of complete dihydropyrimidine dehydrogenase (DPYD) enzyme deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT) with DPYD gene testing mandatory at screening as per national guidelines. UDP-glucuronosyltransferase 1A1 (UGT1A1) testing is not mandatory. However, if UGT test is routinely performed in the participating centers, enrolment of patients carriers of variants of DPYD and homozygous variant UGT1A1 \[7/7\] has to be discussed with the Sponsor.
* Women of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments.
* Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \<1 year after the onset of menopause.
* Men must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods during the treatment period and for at least 7 months after the last administration of study treatments.
* Participants must agree not to donate eggs/sperm for future use for the purposes of assisted reproduction during the study and for a period of 7 months after receiving the last dose of study treatment. Female and male participants should consider preservation of eggs/sperm prior to study treatment as anti-cancer treatments may impair fertility.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rising Tide Foundation

OTHER

Sponsor Role collaborator

Gruppo Oncologico del Nord-Ovest

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Monica Niger, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Locations

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Centro Di Riferimento Oncologico Di Aviano

Aviano, Italy, Italy

Site Status RECRUITING

University Hospital Consorziale Policlinico

Bari, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, Italy, Italy

Site Status NOT_YET_RECRUITING

ASST Ospedale Maggiore di Crema

Crema, Italy, Italy

Site Status RECRUITING

Azienda Socio Sanitaria Territoriale Di Cremona

Cremona, Italy, Italy

Site Status NOT_YET_RECRUITING

Careggi University Hospital

Florence, Italy, Italy

Site Status NOT_YET_RECRUITING

IRCCS Ospedale Policlinico San Martino

Genoa, Italy, Italy

Site Status NOT_YET_RECRUITING

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

Meldola, Italy, Italy

Site Status RECRUITING

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, Italy, Italy

Site Status NOT_YET_RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy, Italy

Site Status NOT_YET_RECRUITING

Istituto Europeo Di Oncologia S.r.l.

Milan, Italy, Italy

Site Status NOT_YET_RECRUITING

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy, Italy

Site Status RECRUITING

Humanitas Istituto Clinico Catanese S.p.A.

Misterbianco, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Sanitaria Locale Napoli 1 Centro

Napoli, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliero-Universitaria Maggiore Della Carità

Novara, Italy, Italy

Site Status NOT_YET_RECRUITING

Istituto Oncologico Veneto

Padua, Italy, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Parma

Parma, Italy, Italy

Site Status NOT_YET_RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Sanitaria Territoriale Di Pesaro E Urbino

Pesaro, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, Italy, Italy

Site Status RECRUITING

Azienda Sanitaria Locale Della Provincia Di Biella

Ponderano, Italy, Italy

Site Status RECRUITING

Azienda USL Toscana Centro

Prato, Italy, Italy

Site Status RECRUITING

Azienda Unita Sanitaria Locale Della Romagna

Ravenna, Italy, Italy

Site Status RECRUITING

I.F.O. Istituti Fisioterapici Ospitalieri

Rome, Italy, Italy

Site Status NOT_YET_RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Italy, Italy

Site Status NOT_YET_RECRUITING

Humanitas Mirasole S.p.A.

Rozzano, Italy, Italy

Site Status NOT_YET_RECRUITING

Pia Fondazione Di Culto E Religione Cardinale Giovanni Panico

Tricase, Italy, Italy

Site Status NOT_YET_RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Italy, Italy

Site Status NOT_YET_RECRUITING

Countries

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Italy

Central Contacts

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Monica Niger, MD

Role: CONTACT

+3902 2390 2919

Facility Contacts

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Elena Ongaro

Role: primary

+390434659050

Francesco Mannavola

Role: primary

+390805592780

Giuseppina Arcangeli

Role: primary

+390303995260

Gianluca Tomasello

Role: primary

+390373280400

Maria Bonomi

Role: primary

+390372405246

Lorenzo Antonuzzo

Role: primary

+390557949648

Roberto Murialdo

Role: primary

+390103538667

Ilario Giovanni Rapposelli

Role: primary

+390543739100

Barbara Galassi

Role: primary

+390255032666

Monica Niger

Role: primary

+3902 2390 2919

Federica Palermo

Role: backup

+3902 2390 3835

Chiara Alessandra Cella

Role: primary

+390257489258

Katia Bruna Bencardino

Role: primary

+390264442291

Carlo Carnaghi

Role: primary

+3909573390900

Laura Attademo

Role: primary

+3908118775339

Laura Giovanna Forti

Role: primary

+3903213732148

Francesca Bergamo

Role: primary

+390498215953

Ingrid Garajovà

Role: primary

+390521702660

Salvatore Corallo

Role: primary

+390382501671

Rita Chiari

Role: primary

+393316893387

Caterina Vivaldi

Role: primary

+39050992466

Francesco Leone

Role: primary

+3901515157503

Samantha Di Donato

Role: primary

+390574802525

Stefano Tamberi

Role: primary

+390544285206

Emanuela Dell'Aquila

Role: primary

+390652666762

Lisa Salvatore

Role: primary

+390630156318

Silvia Bozzarelli

Role: primary

+390282247255

Emiliano Tamburini

Role: primary

+390833773111

Silvio Ken Garattini

Role: primary

+390432554586

Other Identifiers

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2024-515214-41-00

Identifier Type: CTIS

Identifier Source: secondary_id

PANThEON

Identifier Type: -

Identifier Source: org_study_id

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