A Study Evaluating the Efficacy of 5-FU + NALIRI and 5-FU + NALIRINOX for PDAC (NALPAC) (NALPAC)
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| ClinicalTrials.gov Identifier: NCT05472259 |
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Recruitment Status :
Recruiting
First Posted : July 25, 2022
Last Update Posted : July 27, 2022
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Sponsor:
Belgian Group of Digestive Oncology
Collaborator:
University Hospital St Luc, Brussels
Information provided by (Responsible Party):
Belgian Group of Digestive Oncology
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Brief 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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Pancreatic Ductal Adenocarcinoma | Drug: Nanoliposomal irinotecan Drug: 5 FU Drug: Leucovorin Drug: Oxaliplatin | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 134 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 25, 2022 |
| Estimated Primary Completion Date : | June 30, 2025 |
| Estimated Study Completion Date : | December 31, 2027 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm A NALIRI
Cycle length: 14 days Day 1:
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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
Other Name: Onyvide Drug: 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
Other Name: Fluorouracil Drug: 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
Other Names:
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Experimental: Arm B NALIRINOX
Cycle length: 14 days Day 1:
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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
Other Name: Onyvide Drug: 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
Other Name: Fluorouracil Drug: 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
Other Names:
Drug: Oxaliplatin Only administered in the investigational arm (Nalirinox): a dose of 60 mg/m² is administered in combination with nanoliposomal irinotecan, 5FU and Leucovorin |
Primary Outcome Measures :
- Efficacy of NALIRINOX and NALIRI through Progression-Free Survival at D85 [ Time Frame: at day 85 from randomization ]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.
Secondary Outcome Measures :
- Safety/toxicity and tolerability profil: Severety of adverse events [ Time Frame: until 14 days after End of Treatment ]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.
- Safety/toxicity and tolerability profil: Laboratory assessments [ Time Frame: until 14 days after End of Treatment ]
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.
- Safety/toxicity and tolerability profil: ECOG [ Time Frame: until 14 days after End of Treatment ]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.
- Safety/toxicity and tolerability profil: review of body systems [ Time Frame: until 14 days after End of Treatment ]
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
- Progression Free Survival and sensitivity analysis: Effect of Center on prognostic factors [ 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. ]
The effect of potential prognostic factors will be assessed through sensitivity analyses, including:
- Investigational Center
- Progression Free Survival and sensitivity analysis: Effect of tumor location on prognostic factors [ 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 ]
The effect of potential prognostic factors will be assessed through sensitivity analyses, including:
- Location of tumor (head of the pancreas versus other location)
- Progression Free Survival and sensitivity analysis: Effect of previous chemotherapy on prognostic factors [ 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 ]
The effect of potential prognostic factors will be assessed through sensitivity analyses, including:
- Previous chemotherapy: gemcitabine alone vs gem-abx
- Progression Free Survival and sensitivity analysis: effect of ECOG on prognostic factors [ 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 ]
The effect of potential prognostic factors will be assessed through sensitivity analyses, including:
- WHO ECOG performance status (0 versus 1)
- Objective tumor response: Rate of complete response and partial response [ Time Frame: performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks ]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).
- Duration of overall survival [ Time Frame: Time from Day 1 of therapy to death until maximum 5 years after End of Treatment ]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.
- Duration of disease control [ 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 ]Disease control is defined as a best response of either CR, PR, or SD (CR+PR+SD).
- Duration of response [ 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 ]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.
Other Outcome Measures:
- Exploratory lab investigation for potential prognostic and predictive biomarkers on blood and tumor samples [ Time Frame: Sapmples will be collected throughout the study and shipped to the sponsor maximum 1 year after last 15 day follow-up visit ]
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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05472259
Contacts
| Contact: Lina Dewever | +32 (0) 479 36 63 82 | lina.dewever@bgdo.org | |
| Contact: Ine De Bruyne | +32 (0) 478 81 04 27 | i.debruyne@bgdo.org |
Locations
| Belgium | |
| AZ St-Lucas | Not yet recruiting |
| Brugge, West-Vlaanderen, Belgium | |
| Contact: Tania Maerten | |
| Principal Investigator: Liesbeth Holvoet, Dr | |
| UZ Antwerpen | Not yet recruiting |
| Antwerp, Belgium, 2650 | |
| Contact: Sanne Wouters | |
| Principal Investigator: Timon Vandamme, Prof | |
| AZ Imelda | Recruiting |
| Bonheiden, Belgium | |
| Contact: Doreen Iwens | |
| Principal Investigator: Pieter-Jan Cuyle, Dr. | |
| ULB Erasme | Not yet recruiting |
| Brussels, Belgium, 1070 | |
| Contact: Axelle Ghilain | |
| Principal Investigator: Jean-Luc Van Laethem, Dr | |
| Cliniques Universitaires Saint-Luc UCL | Not yet recruiting |
| Brussels, Belgium, 1200 | |
| Contact: Tuan Le | |
| Principal Investigator: Ivan Borbath, Prof | |
| Grand Hopital de Charleroi | Not yet recruiting |
| Charleroi, Belgium | |
| Contact: Matthias Papier | |
| Principal Investigator: Javier Carrasco, Dr. | |
| AZ Maria Middelares | Not yet recruiting |
| Ghent, Belgium | |
| Contact: Margaux Vansteelant | |
| Principal Investigator: Els Monsaert, Dr. | |
| University Hospital Ghent | Not yet recruiting |
| Ghent, Belgium | |
| Contact: Tine Derre | |
| Principal Investigator: Karen Geboes, Prof. | |
| CHC MontLégia | Not yet recruiting |
| Liège, Belgium, 4000 | |
| Contact: Jocelyne Gilson | |
| Principal Investigator: Ghislain Houbiers, Dr | |
| AZ Sint-Maarten | Not yet recruiting |
| Mechelen, Belgium | |
| Contact: Katrien Beullens | |
| Principal Investigator: Leen Mortier, Dr. | |
| CHU Ambroise Paré | Not yet recruiting |
| Mons, Belgium | |
| Contact: Mariane Blockmans | |
| Principal Investigator: Marie Diaz, Dr. | |
| CHR Namur | Not yet recruiting |
| Namur, Belgium | |
| Contact: Christine Leon | |
| Principal Investigator: Yeter Gokburun, Dr. | |
Sponsors and Collaborators
Belgian Group of Digestive Oncology
University Hospital St Luc, Brussels
Investigators
| Principal Investigator: | Ivan Borbath | University hospital St-luc, Brussel |
| Responsible Party: | Belgian Group of Digestive Oncology |
| ClinicalTrials.gov Identifier: | NCT05472259 |
| Other Study ID Numbers: |
NALPAC |
| First Posted: | July 25, 2022 Key Record Dates |
| Last Update Posted: | July 27, 2022 |
| Last Verified: | July 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Leucovorin Fluorouracil Oxaliplatin Irinotecan Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic |
Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Antidotes Protective Agents Vitamin B Complex Vitamins Micronutrients |