2nd-line Therapy With Nal-IRI After Gem/Nab-pac in Advanced Pancreatic Cancer - Predictive Role of 1st-line Therapy

NCT03468335 | Completed Phase 3

• 1 other identifier: AIO-PAK-0216
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 35

Brief Summary

Second-line therapy with Nal-IRI after failure gemcitabine/nab-paclitaxel in advanced pancreatic cancer - predictive role of 1st-line therapy

Conditions

Locally Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer

Keywords

Second-line therapy; Nal-IRI; failure gemcitabine/nab-paclitaxel; predictive role of 1st-line therapy

Outcome Measures

Primary Outcomes (1)

• Time to Treatment Failure of second-line treatment (TTF2)

  Time-To-Treatment-Failure - (TTF2) is defined as date of signed ICF until permanent treatment discontinuation (or day of initially planned next cycle) due to progressive disease or unacceptable toxicity. Expected increase of the TTF2 by 50% in the cohort of patients with favorable TTF1 (TTF1 high: upper third of the patient population) as compared to patients with short TTF1 (TTF low: lowest third of the patient population)

  up to 6 month

Secondary Outcomes (8)

• Overall survival (OS)

  up to 12 month

• Progression Free Survival (PFS)

  up to 12 month

• AEs / SAEs

  up to 12 month

• Quality of Life (QoL) EORTC QLQ-C30

  up to 6 month

• Quality of Life (QoL) EORTC QLQ-PAN26

  up to 6 month

Study Arms (1)

Single Arm

OTHER

Cancer treatment for PDAC: * Nal-IRI (4.3 mg/ml) 70 mg/m2 as 1.5 hour infusion * 5-FU 2400 mg/m2 as 46 hour infusion * Folinic acid 400 mg/m2 as 0.5 hour infusion * all on D1 of each cycle; Cycle q2w ± 5 days Treatment until progressive disease or intolerable toxicity or withdrawal of consent.

Drug: Irinotecan Liposomal Injection [Onivyde]

Interventions

Irinotecan Liposomal Injection [Onivyde] DRUG

Cancer treatment for PDAC: * Nal-IRI (4.3 mg/ml) 70 mg/m2 as 1.5 hour infusion * 5-FU 2400 mg/m2 as 46 hour infusion * Folinic acid 400 mg/m2 as 0.5 hour infusion * all on D1 of each cycle; Cycle q2w ± 5 days Treatment until progressive disease or intolerable toxicity or withdrawal of consent.

Also known as: Nal-IRI

Single Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent including participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Clinical indication for a 2nd-line systemic therapy according to current standard-of-care.
• Age ≥ 18 years at time of study entry
• Patients with histologically or cytologically confirmed pancreatic ductal adenocarcinoma
• ECOG performance status 0-2
• One line of systemic gemcitabine/Nab-paclitaxel -based therapy for advanced disease (irrespective of prior adjuvant therapy) OR Previous adjuvant gemcitabine/Nab-paclitaxel-based chemotherapy with documented progression less than 6 months after termination
• Detailed documentation of prior therapy (duration, dose-intensity, maximum toxicity, reason for discontinuation)
• Adequate blood count, liver-enzymes, and renal function:
• neutrophil count \> 1.5 x 10\^6/mL
• Platelet count ≥ 100 x 10\^9/L (≥100,000 per mm\^3)
• AST (SGOT)/ALT (SGPT) ≤ 5 x institutional upper limit of normal
• bilirubin ≤1.5 ULN (\<3 x ULN in patients with confirmed mechanical cholestasis)
• Creatinine Clearance CLcr ≥ 30 mL/min
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if:

• Medical criteria:
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:
• Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes
• Premalignant hematologic disorders, e.g. myelodysplastic syndrome
• Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
• Prior (\<3 years) or concurrent malignancy (other than biliary-tract cancer) which either progresses or requires active treatment. Exceptions are: basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a or T1b prostate carcinoma, or superficial urinary bladder tumor \[Ta, Tis and T1\].
• Pre-existing lung disease of clinical significance or with impact on performance status
• History or clinical evidence of CNS metastases
• Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria:
• I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of study treament. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases
• Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy
• Severe non-healing wounds, ulcers or bone fractions
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedures, except open biopsy, or significant traumatic injury within 28 days prior to star of study treatment, or anticipation of the need for major surgical procedure during the course of the study except for surgery of central intravenous line placement for chemotherapy administration.
• Known Gilbert-Meulengracht syndrome

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Crolll Gmbh: collaborator
• Servier Deutschland GmbH: collaborator

Study Sites (35)

Klinikum St. Marien Amberg

Amberg, 92224, Germany

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Hämatologisch-Onkologische Gemeinschaftspraxis

Bad Soden, 65812, Germany

Location

St.Josef-Hospital Klinikum der Ruhr-Universität Bochum

Bochum, 44791, Germany

Location

Städtisches Klinikum Brandenburg

Brandenburg, 14770, Germany

Location

MVZ Klinikum Coburg GmbH

Coburg, 96450, Germany

Location

Uniklinikum Köln GmbH

Cologne, 50937, Germany

Location

Donauisar Klinikum

Deggendorf, 94469, Germany

Location

BAG Onkologische Gemeinschaftspraxis Dresden

Dresden, 01307, Germany

Location

MVZ Onkologische Kooperation Harz

Goslar, 38642, Germany

Location

Medi Projekt

Hanover, 30171, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

DRK-Kliniken Nordhessen

Kassel, 34121, Germany

Location

St. Elisabeth-Krankenhaus GmbH

Köln - Hohenlind, 50935, Germany

Location

Klinikum Landshut gGmbH

Landshut, 84034, Germany

Location

Onkopraxis Probstheida

Leipzig, 04289, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Uniklinikum Marburg

Marburg, 35043, Germany

Location

Krankenhaus Neuperlach

München, 81737, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, 90419, Germany

Location

Ambulantes Therapiezentrum Hämatologie / Onkologie

Offenburg, 77654, Germany

Location

Pius-Hospital

Oldenburg, 26121, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Elblandklinikum Riesa

Riesa, 01589, Germany

Location

Klinikum Südstadt Rostock

Rostock, 18059, Germany

Location

Caritas-Klinik St. Theresia

Saarbrücken, 66113, Germany

Location

Diakonie Klinikum gGmbH

Schwäbisch Hall, 74523, Germany

Location

Leopoldina Krankenhaus

Schweinfurt, 97422, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar-Klinikum

Villingen-Schwenningen, 78052, Germany

Location

Kliniken Nordoberpfalz Klinikum Weiden

Weiden, 92637, Germany

Location

Medizinische Studiengesellschaft Onkologie Nord-West GmbH

Westerstede, 26655, Germany

Location

St. Josefs-Hospital

Wiesbaden, 65189, Germany

Location

Hämatologisch-Onkologische Praxis Würselen

Würselen, 52146, Germany

Location

Related Publications (2)

• Lutz MP, Ansorge N, Barmashenko G, Bauer H, Burkart C, Decker T, Ettrich T, Fischer von Weikersthal L, Geer T, Gerhardt A, Hofling S, Jacobasch L, Koenigsmann M, Leidig T, Plentz R, Rath S, Reichert D, Schulte M, Schulte N, Schwarzer A, Siegler G, Waldschmidt D, Karthaus M. Predictive criteria for overall survival and treatment duration of 2nd-line chemotherapy in patients with advanced pancreatic adenocarcinoma (AIO-PAK-0216). Br J Cancer. 2026 Jan;134(1):85-91. doi: 10.1038/s41416-025-03188-x. Epub 2025 Oct 14.

  PMID: 41087530 DERIVED

• Lahusen A, Lutz MP, Fang R, Kirchner M, Albus S, Kluck K, Karthaus M, Schwarzer A, Siegler G, Kleger A, Ettrich TJ, Becher A, Hofling S, Siveke JT, Budczies J, Tannapfel A, Stenzinger A, Cheung PF, Eiseler T, Seufferlein T. An immune responsive tumor microenvironment imprints into PBMCs and predicts outcome in advanced pancreatic cancer: lessons from the PREDICT trial. Mol Cancer. 2025 Jul 22;24(1):202. doi: 10.1186/s12943-025-02406-7.

  PMID: 40696453 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

irinotecan sucrosofate

Condition Hierarchy (Ancestors)

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

Study Officials

• Manfred P. Lutz, Prof. Dr.

  m.lutz@caritasklinikum.de

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open label, single arm, multicenter phase IIIb trial

Study Record Dates

• First Submitted: January 19, 2018
• First Posted: March 16, 2018
• Study Start: March 31, 2018
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: April 17, 2025

Record last verified: 2025-04

Locations

DE (35)