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

Metastatic Pancreatic Ductal Adenocarcinoma Clinical Trial

— NALPAC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05472259
• Other study ID #: NALPAC
• Status: Recruiting
• Phase: Phase 2
• Start date: May 25, 2022
• Est. completion date: December 31, 2027

Study information

• Verified date: July 2022
• Source: Belgian Group of Digestive Oncology
• Contact: Lina Dewever
• Phone: +32 (0) 479 36 63 82
• Email: lina.dewever[@]bgdo.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 134
• Est. completion date: December 31, 2027
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• 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
• 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
• 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
• Oxaliplatin
Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin

Locations

Country	Name	City	State
Belgium	UZ Antwerpen	Antwerp
Belgium	AZ Imelda	Bonheiden
Belgium	AZ St-Lucas	Brugge	West-Vlaanderen
Belgium	Cliniques Universitaires Saint-Luc UCL	Brussels
Belgium	ULB Erasme	Brussels
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	AZ Maria Middelares	Ghent
Belgium	University Hospital Ghent	Ghent
Belgium	CHC MontLégia	Liège
Belgium	AZ Sint-Maarten	Mechelen
Belgium	CHU Ambroise Paré	Mons
Belgium	CHR Namur	Namur

Sponsors (2)

Lead Sponsor	Collaborator
Belgian Group of Digestive Oncology	University Hospital St Luc, Brussels

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory lab investigation for potential prognostic and predictive biomarkers on blood and tumor samples	Translational research will be performed for potential prognostic and predictive biomarkers. For that purpose, plasma samples will be kept in the selected centres' biobanks.; The translational research will be carried out on tumor samples collected before the start of treatment and on blood samples collected as per below.; Tumor tissue: 10 slices of the paraffin embedded tissue collected during the diagnosis of the disease will be collected.; Blood samples: Two 10 ml blood samples from each patient who consents to participate in the biological study will be collected before the start of the treatment, and before each cycle till the discontinuation of the treatment.; The exact measurements that will be done, have not been defined yet.	Sapmples will be collected throughout the study and shipped to the sponsor maximum 1 year after last 15 day follow-up visit
Primary	Efficacy 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.	at day 85 from randomization
Secondary	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.	until 14 days after End of Treatment
Secondary	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.	until 14 days after End of Treatment
Secondary	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.	until 14 days after End of Treatment
Secondary	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	until 14 days after End of Treatment
Secondary	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	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.
Secondary	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)	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
Secondary	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	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
Secondary	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)	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
Secondary	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).	performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks
Secondary	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 from Day 1 of therapy to death until maximum 5 years after End of Treatment
Secondary	Duration of disease control	Disease control is defined as a best response of either CR, PR, or SD (CR+PR+SD).	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
Secondary	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 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