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
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
134
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
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
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
UZ Antwerpen
Antwerp, Antwerp, Belgium
RECRUITINGULB Erasme
Brussels, Brussels Capital, Belgium
RECRUITINGEfficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85
NALIRINOX is the investigational arm and NALIRI is the standard care arm. The efficacy will be assessed in terms of the Progression-Free Survival Rate (PFSR). This is defined as the proportion of patients alive and free of progression at day 85.
Time frame: at day 85 from randomization
Safety/toxicity and tolerability profil: Severety of adverse events
Adverse events and Serious Adverse events will be assessed during the study treatment and until 14 days later. Severety will be graded according to the NCI-CTCAE version 5.0 and relationship to the study medication will be defined.
Time frame: until 14 days after End of Treatment
Safety/toxicity and tolerability profil: Laboratory assessments
Standard laboratory safety assessments: They are mandatory prior to each administration of study medication and at the 15 days follow-up visit. Clinically significant vs not clinically significant.
Time frame: until 14 days after End of Treatment
Safety/toxicity and tolerability profil: ECOG
WHO ECOG performance status (PS) will be defined prior to each administration of study medication and at the 15 days follow-up visit following the ECOG Performance Status Scale.
Time frame: until 14 days after End of Treatment
Safety/toxicity and tolerability profil: review of body systems
A full review of body systems will be performed: heart rate, blood pressure, respiratory rate, body temperature, height, weight and ECG (screening visit only, unless clinically indicated). Clinically significant versus not clinically significant
Time frame: until 14 days after End of Treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin
Cliniques Universitaires Saint-Luc UCL
Brussels, Brussels Capital, Belgium
RECRUITINGCHC MontLégia
Liège, Liège, Belgium
RECRUITINGAZ St-Lucas
Bruges, West-Vlaanderen, Belgium
NOT_YET_RECRUITINGAZ Imelda
Bonheiden, Belgium
RECRUITINGGrand Hopital de Charleroi
Charleroi, Belgium
RECRUITINGAZ Maria Middelares
Ghent, Belgium
RECRUITINGUniversity Hospital Ghent
Ghent, Belgium
RECRUITINGPôle Hospitalier Jolimont (HELORA)
Haine-Saint-Paul, Belgium
RECRUITING...and 3 more locations
Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors
The effect of potential prognostic factors will be assessed through sensitivity analyses, including: * Investigational Center
Time frame: 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
The effect of potential prognostic factors will be assessed through sensitivity analyses, including: * Location of tumor (head of the pancreas versus other location)
Time frame: 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
The effect of potential prognostic factors will be assessed through sensitivity analyses, including: * Previous chemotherapy: gemcitabine alone vs gem-abx
Time frame: 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
The effect of potential prognostic factors will be assessed through sensitivity analyses, including: * WHO ECOG performance status (0 versus 1)
Time frame: 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
Tumor (response) evaluation will be performed according to RECIST criteria v. 1.1 (CT scan thorax, abdomen and pelvis or MRI abdomen and pelvis + CT chest) based upon the investigator's assessment. Overall response is defined as a best response of either CR or PR (CR+PR).
Time frame: performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks
Duration of overall survival
For patients who are still alive at the time of study analysis or who are lost to follow up, survival will be censored at the last recorded date that the patient is known to be alive or at the date of data cut-off, whatever occurs earlier.
Time frame: Time from Day 1 of therapy to death until maximum 5 years after End of Treatment
Duration of disease control
Disease control is defined as a best response of either CR, PR, or SD (CR+PR+SD).
Time frame: 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
The duration of response will be censored on the date of last known tumor assessment for not progressed patients lost to follow up or deceased prior to the next planned tumor assessment (within 60 days). Not evaluable patients at one time point assessment will be censored at the date of last known assessment.
Time frame: 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