| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Pancreatic ductal adenocarcinoma (PDAC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pancreatic ductal adenocarcinoma. This is a type of exocrine pancreatic cancer. It is the most common type of pancreatic cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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). The PFSR is defined as the proportion of patients alive and free of progression at day 85.
|
|
| E.2.2 | Secondary objectives of the trial |
To evaluate in both treatment 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)
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Translational research will be performed for potential prognostic and predictive biomarkers. For that purpose, plasma samples will be kept in the selected centres’ biobanks, based on a selection of voluntary centres by the BGDO.
The translational research will be carried out on tumor samples collected before the start of treatment and on blood samples collected as per below.
|
|
| E.3 | Principal inclusion criteria |
1. Histologically proven metastatic adenocarcinoma of the pancreas
2. Progression documented after Gemcitabine-Abraxane or gemcitabine alone
3. Signed written informed consent
4. Age ≥ 18
5. ECOG PS 0/1 at study entry
6. Measurable disease
7. 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)
8. INR/PTT ≤ 1.5x ULN
9. Life expectancy of at least 12 weeks
10. Effective contraception for both male and female patients if the risk of conception exists
11. Peripheral Neuropathy < grade 2
|
|
| E.4 | Principal exclusion criteria |
1. Uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
2. History of myocardial infarction, deep venous or arterial thrombosis, CVA during the last 6 months
3. Known hypersensitivity to any of the components of study treatments
4. Previous malignancy in the last past 3 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or carcinoma in situ of any type
5. Pregnancy or breast feeding
6. Medical or psychological conditions that would not permit the patient to complete the study or sign inform consent
7. Unstable angina, congestive heart failure ≥NYHA class II
8. Uncontrolled hypertension despite optimal management (systolic blood pressure >150 mmHg or diastolic pressure > 90mmHg)
9. Complete DPD deficiency
10. HIV infection
11. Liver failure, cirrhosis Child Pugh B or C
12. Active chronic hepatitis B or C with a need for antiviral treatment
13. Brain metastasis
14. Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
15. History of organ allograft
16. Ongoing uncontrolled, serious infection
17. Renal failure requiring dialysis
18. Patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
PFSR is defined as the proportion of patients alive and free of progression at day 85. Patients who do not progress are considered achieving either a stable disease (SD), a partial response (PR) or a complete response (CR) at day 85, according to RECIST 1.1 criteria. Patients who are unable to be evaluated at day 85, due to rapid clinical deterioration or death from any cause or start of an additional anti-tumor therapy, will be considered as progressive disease (PD).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFSR is defined as the proportion of patients alive and free of progression at day 85. Patients who do not progress are considered achieving either a stable disease (SD), a partial response (PR) or a complete response (CR) at day 85, according to RECIST 1.1 criteria. Patients who are unable to be evaluated at day 85, due to rapid clinical deterioration or death from any cause or start of an additional anti-tumor therapy, will be considered as progressive disease (PD).
|
|
| E.5.2 | Secondary end point(s) |
• Safety/toxicity and tolerability profile
Safety/toxicity and tolerability will be assessed throughout the study by evaluating the following safety variables:
o Adverse events throughout the study for which the following data are to be recorded:
Description
Start and stop date and time
NCI-CTCAE v. 5
Grade
Causal relationship with medication
Action taken
Outcome
Seriousness
Expectedness
o Laboratory safety assessments performed as specified in 6.6.4 Lab assessments. They are mandatory prior to the administration of study medication. Tumor markers CA 19-9 and CEA are measured at baseline, every 6 weeks for 3 times, then every 8 weeks until progression or withdrawal and at the follow-up visit.
o Physical examination as described at section 6.6.3 and WHO ECOG performance status (PS)
• PFS and sensitivity analyses
• PFS is defined as the time from Day 1 of therapy (day of first infusion of medication on study), until the first observation of disease progression according RECIST 1.1 criteria or the date of death due to any cause.
• For patients who deceased more than 60 days after either the last valid tumor assessment or after the date of Day 1 of therapy without having had imaging performed, the PFS time will be censored on the date of last tumor assessment or date of Day 2 of therapy respectively.
• Non-progressed patients discontinuing study treatment and not undertaking a different anti-cancer treatment will be censored for progression at the date of the last valid tumor assessment.
• Non-progressed patients discontinuing study treatment and undertaking a different anti-cancer treatment will be censored for progression at the date of starting the new anti-cancer treatment. Exceptions of this rule may be applied for patients undertaking procedures that are not aimed at the main disease i.e. stenting, radiotherapy for symptom control not on target lesions, and possibly other treatments on a case by case basis
• The effect of potential prognostic factors will be assessed through sensitivity analyses, including:
Center
WHO ECOG performance status (0 versus 1)
Location of tumor (head of the pancreas versus other location)
Previous chemotherapy: gemcitabine alone vs gem-abx
• Objective tumor response:
Tumor (response) evaluation will be performed within 28 days before start therapy, 3 times every 6 weeks and afterwards every 8 weeks, 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).
• Overall survival:
The survival time of a patient is defined as the time from Day 1 of therapy to death. 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.
• Disease control:
Disease control is defined as a best response of either CR, PR, or SD (CR+PR+SD).
• Duration of response:
The duration of response in responding patients is defined as the time interval from the time 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). 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.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
Print
