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

NCT ID: NCT03468335

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-31
• Study Completion Date: 2022-05-31

Brief Summary

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

Detailed Description

Research hypothesis:

Patients profit from 2nd-line therapy with Nal-IRI if they also had a benefit from 1st-line treatment. Benefit from treatment (either 1st or 2nd-line) will be defined as a patient specific Time-To-Treatment Failure (TTF) which is in the upper third of the distribution of TTF values of the studied population.

Conditions

Locally Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm

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.

Group Type: OTHER

Irinotecan Liposomal Injection [Onivyde]

Intervention Type: 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.

Interventions

Irinotecan Liposomal Injection [Onivyde]

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.

Intervention Type: DRUG

Other Intervention Names

Nal-IRI

Eligibility Criteria

Inclusion Criteria

1. 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

2. Clinical indication for a 2nd-line systemic therapy according to current standard-of-care.

3. Age ≥ 18 years at time of study entry

4. Patients with histologically or cytologically confirmed pancreatic ductal adenocarcinoma

5. Imaging of evaluable lesions within 2 weeks of inclusion (either sonography, X-ray, CT scans, MRI)

6. ECOG performance status 0-2

7. 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

8. Detailed documentation of prior therapy (duration, dose-intensity, maximum toxicity, reason for discontinuation)

9. 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

10. 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.

Exclusion Criteria

Medical criteria:

1. 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:

1. Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes

2. Premalignant hematologic disorders, e.g. myelodysplastic syndrome

3. Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment

4. 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].

5. Pre-existing lung disease of clinical significance or with impact on performance status

6. 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

7. Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy

8. Severe non-healing wounds, ulcers or bone fractions

9. Evidence of bleeding diathesis or coagulopathy

10. 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.

11. Known Gilbert-Meulengracht syndrome

12. Known chronic hypoacusis, tinnitus or vertigo

13. Bone marrow depression (e.g., after radiation therapy)

14. Pernicious anemia and other megaloblastic anemias secondary to vitamin B12 deficiency

15. Severe impairment of hepatic function

16. Diarrhea

Drug related criteria:

2. Medication that is known to interfere with any of the agents applied in the trial.

3. Known dihydropyrimidine dehydrogenase (DPD) deficiency

4. History of hypersensitivity to any of the study drugs or any of the constituents of the products.

5. Any other efficacious cancer treatment except protocol specified treatment at study start.

Safety criteria:

6. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (urine or serum β-HCG acc. to SOC) at Screening.

Methodological criteria:

7. Any experimental pretreatment for advanced disease

8. Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.

9. Previous enrollment in the present study (does not include screening failure).

Regulatory and ethical criteria:

10. Patient who might be dependent on the sponsor, site or the investigator

11. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Crolll Gmbh

OTHER

Sponsor Role: collaborator

Servier Deutschland GmbH

INDUSTRY

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Manfred P. Lutz, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

m.lutz@caritasklinikum.de

Locations

Klinikum St. Marien Amberg

Amberg, , Germany

HELIOS Klinikum Bad Saarow

Bad Saarow, , Germany

Hämatologisch-Onkologische Gemeinschaftspraxis

Bad Soden, , Germany

St.Josef-Hospital Klinikum der Ruhr-Universität Bochum

Bochum, , Germany

Städtisches Klinikum Brandenburg

Brandenburg, , Germany

MVZ Klinikum Coburg GmbH

Coburg, , Germany

Uniklinikum Köln GmbH

Cologne, , Germany

Donauisar Klinikum

Deggendorf, , Germany

BAG Onkologische Gemeinschaftspraxis Dresden

Dresden, , Germany

MVZ Onkologische Kooperation Harz

Goslar, , Germany

Medi Projekt

Hanover, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

DRK-Kliniken Nordhessen

Kassel, , Germany

St. Elisabeth-Krankenhaus GmbH

Köln - Hohenlind, , Germany

Klinikum Landshut gGmbH

Landshut, , Germany

Onkopraxis Probstheida

Leipzig, , Germany

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, , Germany

Universitätsmedizin Mannheim

Mannheim, , Germany

Uniklinikum Marburg

Marburg, , Germany

Krankenhaus Neuperlach

München, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Ambulantes Therapiezentrum Hämatologie / Onkologie

Offenburg, , Germany

Pius-Hospital

Oldenburg, , Germany

Studienzentrum Onkologie Ravensburg

Ravensburg, , Germany

Elblandklinikum Riesa

Riesa, , Germany

Klinikum Südstadt Rostock

Rostock, , Germany

Caritas-Klinik St. Theresia

Saarbrücken, , Germany

Diakonie Klinikum gGmbH

Schwäbisch Hall, , Germany

Leopoldina Krankenhaus

Schweinfurt, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Schwarzwald-Baar-Klinikum

Villingen-Schwenningen, , Germany

Kliniken Nordoberpfalz Klinikum Weiden

Weiden, , Germany

Medizinische Studiengesellschaft Onkologie Nord-West GmbH

Westerstede, , Germany

St. Josefs-Hospital

Wiesbaden, , Germany

Hämatologisch-Onkologische Praxis Würselen

Würselen, , Germany

Countries

Germany

References

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. 2025 Oct 14. doi: 10.1038/s41416-025-03188-x. Online ahead of print.

Reference Type: DERIVED

PMID: 41087530 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40696453 (View on PubMed)

Other Identifiers

AIO-PAK-0216

Identifier Type: -

Identifier Source: org_study_id