A Study Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for PDAC (NALPAC)

Официальное название

A Non-comparative Randomized Phase 2 Study, Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC), Progressive After Gemcitabine-Abraxane or Gemcitabine Monotherapy

Обзор

A non-comparative randomized phase 2 study, evaluating the efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for metastatic pancreatic ductal adenocarcinoma (PDAC), progressive after Gemcitabine-Abraxane or Gemcitabine monotherapy

Подробное описание

Based on the results of previous studies, the sponsor aims to assess efficacy and safety of this triplet (irinotecan, 5FU/LV and oxaliplatin) in second-line treatment in fit patients (ECOG 0-1) metastatic PDAC.

The primary objective is to assess the efficacy of NALIRINOX (= investigational arm) and NALIRI (= standard care arm) in terms of Progression-Free Survival Rate (PFSR).

As secondary objectives, the following will be evaluated in both arms:

* Safety/toxicity and tolerability profile according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5. * Progression free survival (PFS) * Overall response rate and duration of response as assessed by imaging (RECIST 1.1) and tumor markers * Overall survival (OS)

Вмешательства

• Препарат Nanoliposomal irinotecan
  In the control arm (Naliri) a dose of 70mg/m² is administered in combination with 5FU and leucovorin In the investigational arm (Nalirinox) a dose of 50mg/m² is administered in combination with 5FU, leucovorin and oxaliplatin
• Препарат 5 FU
  In the control arm (Naliri) a dose of 2400 mg/m² is administered in combination with nanoliposomal irinotecan and leucovorin In the investigational arm (Nalirinox) a dose of 2400 mg/m² is administered in combination with nanoliposomal irinotecan, leucovorin and oxaliplatin
• Препарат Leucovorin
  In the control arm (Naliri) a dose of 400 mg/m² is administered in combination with nanoliposomal irinotecan and 5FU In the investigational arm (Nalirinox) a dose of 400 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and oxaliplatin
• Препарат Oxaliplatin
  Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin

Первичные конечные точки

• Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85 [Срок оценки: at day 85 from randomization]

Вторичные конечные точки (12)

• Safety/toxicity and tolerability profil: Severety of adverse events [Срок оценки: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: Laboratory assessments [Срок оценки: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: ECOG [Срок оценки: until 14 days after End of Treatment]
• Safety/toxicity and tolerability profil: review of body systems [Срок оценки: until 14 days after End of Treatment]
• Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors [Срок оценки: From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment.]
• Progression Free Survival and sensitivity analysis: Effect of tumor location on prognostic factors [Срок оценки: From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment]
• Progression Free Survival and sensitivity analysis: Effect of previous chemotherapy on prognostic factors [Срок оценки: From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment]
• Progression Free Survival and sensitivity analysis: effect of ECOG on prognostic factors [Срок оценки: From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment]
• Objective tumor response: Rate of complete response and partial response [Срок оценки: performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks]
• Duration of overall survival [Срок оценки: Time from Day 1 of therapy to death until maximum 5 years after End of Treatment]
• Duration of disease control [Срок оценки: From date of first study treatment administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years after End of Treatment]
• Duration of response [Срок оценки: Time from measurement criteria are first met for CR/PR to either the first time disease progression is documented or death (for not progressed patients who deceased within 60 days from last tumor assessment) until maximum 5 years after EOT]

Критерии участия

Критерии включения

• Histologically proven metastatic adenocarcinoma of the pancreas
• Progression documented after gemcitabine-Abraxane, or gemcitabine monotherapy
• Signed written informed consent
• Age ≥ 18
• ECOG PS 0/1 at study entry
• Measurable disease
• Adequate renal (serum creatinine ≤ 1.5x upper reference range), liver (total bilirubin ≤ 1.5x upper reference range) and hematopoietic functions (PMN ≥ 1,5x109/L, platelets ≥ 100x109/L, hemoglobin ≥ 9g/dl)
• INR/PTT ≤ 1.5x ULN
• Life expectancy of at least 12 weeks
• Effective contraception for both male and female patients if the risk of conception exists during treatment and for one month after the last administration
• Peripheral Neuropathy < grade 2

Критерии исключения

• Uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
• History of myocardial infarction, deep venous or arterial thrombosis, CVA during the last 6 months
• Known hypersensitivity to any of the components, including excipients, of study treatments
• Previous malignancy in the last past 3 years except basal cell cancer of the skin or preinvasive cancer of the cervix or carcinoma in situ of any type
• Pregnancy or breast feeding
• Medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
• Unstable angina, congestive heart failure ≥NYHA class II
• Uncontrolled hypertension despite optimal management (systolic blood pressure >150 mmHg or diastolic pressure > 90mmHg)
• HIV infection
• Complete DPD deficiency
• Liver failure, cirrhosis Child Pugh B or C
• Active chronic hepatitis B or C with a need for antiviral treatment
• Brain metastasis
• Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
• History of organ allograft
• Ongoing uncontrolled, serious infection
• Renal failure requiring dialysis
• Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бельгия · 13 центров

• UZ Antwerpen — Antwerp
• ULB Erasme — Brussels
• Cliniques Universitaires Saint-Luc UCL — Brussels
• CHC MontLégia — Liège
• AZ St-Lucas — Bruges
• AZ Imelda — Bonheiden
• Grand Hopital de Charleroi — Charleroi
• AZ Maria Middelares — Ghent
• … и ещё 5 центров

Идентификаторы

NCT: NCT05472259 · NALPAC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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