Clinical trial NCT03468335: 2nd-line Therapy With Nal-IRI After Gem/Nab-pac in Advanced Pancreatic Cancer - Predictive Role of 1st-line Therapy
Official title: Second-line Therapy With Nal-IRI After Failure Gemcitabine/Nab-paclitaxel in Advanced Pancreatic Cancer - Predictive Role of 1st-line Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Locally Advanced Pancreatic Cancer
Metastatic Pancreatic Cancer
Keywords: Second-line therapy
Nal-IRI
failure gemcitabine/nab-paclitaxel
predictive role of 1st-line therapy
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
Collaborators: name: Crolll Gmbh
name: Servier Deutschland GmbH
First posted: 2018-03-16
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, single arm, multicenter phase IIIb trial
Primary purpose: TREATMENT

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.

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 \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\].

Primary outcomes:
measure: Time to Treatment Failure of second-line treatment (TTF2)
timeFrame: up to 6 month
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to 12 month
measure: Progression Free Survival (PFS)
timeFrame: up to 12 month
measure: AEs / SAEs
timeFrame: up to 12 month
measure: Quality of Life (QoL) EORTC QLQ-C30
timeFrame: up to 6 month
measure: Quality of Life (QoL) EORTC QLQ-PAN26
timeFrame: up to 6 month
measure: Quality of Life (QoL) EORTC EQ-5D-5L
timeFrame: up to 6 month
measure: Evaluation of time to definitive deterioration of QoL (TDD)
timeFrame: from date of baseline Scrore until date QoL Score deterioration, assessed up to 12 month
measure: Growth modulation index (GMI)
timeFrame: up to 6 month
Other outcomes:
Locations:
city: Amberg
country: Germany
facility: Klinikum St. Marien Amberg
city: Bad Saarow
country: Germany
facility: HELIOS Klinikum Bad Saarow
city: Bad Soden
country: Germany
facility: Hämatologisch-Onkologische Gemeinschaftspraxis
city: Bochum
country: Germany
facility: St.Josef-Hospital Klinikum der Ruhr-Universität Bochum
city: Brandenburg
country: Germany
facility: Städtisches Klinikum Brandenburg
city: Coburg
country: Germany
facility: MVZ Klinikum Coburg GmbH
city: Deggendorf
country: Germany
facility: Donauisar Klinikum
city: Dresden
country: Germany
facility: BAG Onkologische Gemeinschaftspraxis Dresden
city: Goslar
country: Germany
facility: MVZ Onkologische Kooperation Harz
city: Hannover
country: Germany
facility: Medi Projekt
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Kassel
country: Germany
facility: DRK-Kliniken Nordhessen
city: Köln - Hohenlind
country: Germany
facility: St. Elisabeth-Krankenhaus GmbH
city: Köln
country: Germany
facility: Uniklinikum Köln GmbH
city: Landshut
country: Germany
facility: Klinikum Landshut gGmbH
city: Leipzig
country: Germany
facility: Onkopraxis Probstheida
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein gGmbH
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Marburg
country: Germany
facility: Uniklinikum Marburg
city: München
country: Germany
facility: Krankenhaus Neuperlach
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Offenburg
country: Germany
facility: Ambulantes Therapiezentrum Hämatologie / Onkologie
city: Oldenburg
country: Germany
facility: Pius-Hospital
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
city: Riesa
country: Germany
facility: Elblandklinikum Riesa
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock
city: Saarbrücken
country: Germany
facility: Caritas-Klinik St. Theresia
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus
city: Schwäbisch Hall
country: Germany
facility: Diakonie Klinikum gGmbH
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar-Klinikum
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz Klinikum Weiden
city: Westerstede
country: Germany
facility: Medizinische Studiengesellschaft Onkologie Nord-West GmbH
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital
city: Würselen
country: Germany
facility: Hämatologisch-Onkologische Praxis Würselen
Study officials:
affiliation: m.lutz@caritasklinikum.de
name: Manfred P. Lutz, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: