E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Pancreatic Ductal Adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
Evaluate the superiority in terms Overall Survival (OS) of gemcitabine + solvent-based (sb)-paclitaxel over gemcitabine alone in metastatic pancreatic ductal adenocarcinoma after FOLFIRINOX failure or intolerance. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are the evaluation of:
- The efficacy of the treatments in terms of:
*Objective Response rate (according to RECIST 1.1) (ORR)
*Progression-Free Survival (PFS)
*Disease Control Rate at 4 months (4m-DCR)
- Prognostic and predictive values of several biomarkers (Ca 19-9, CEA, neutrophil to lymphocyte ratio, albumin, Glasgow prognostic score)
- Dose intensity of chemotherapy
- Safety and tolerability of treatment (NCI-CTCAE version 5.0)
- The effect of treatments on Quality of Life
- The rate of subsequent chemotherapy (after progression)
- Potential new biomarkers that may provide relevant information for clinicians as to whether the patients benefit from chemotherapy and to study the biomarkers dynamics across time and their association with primary and secondary endpoints of the trial. |
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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 |
Analysis of constitutional DNA and circulating tumor DNA to observ correlation of tumor molecular biomarkers with clinical outcomes. |
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E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC).
2. Age ≥18 years old.
3. At least one evaluable lesion according to RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) outside any previously irradiated area.
4. Failure of first line FOLFIRINOX therapy due to progressive disease during or within 3 months after the end of therapy (including mFOLFIRINOX in adjuvant setting) or patient with FOLFIRINOX intolerance
5. Performance Status (PS) ECOG 0 to 2.
6. Life expectancy ≥12 weeks.
7. Negative serology (HIV, hepatitis B and C)
8. Adequate organs function:
- Absolute neutrophils count ≥1.5x109/L
- Platelets count ≥100x109/L
- Haemoglobin ≥9 g/dl
- Serum bilirubin levels <2 times upper limit of normal (ULN), up to 2.5 times ULN in case of hepatic metastasis (biliary drainage allowed)
- Transaminases <5 times ULN.
9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
10. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment/therapy
11. Patients affiliated to the social security system
12. Patient must have signed a written informed consent form prior to any trial specific procedures |
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E.4 | Principal exclusion criteria |
1. Any other primary tumor or secondary malignancy except basal cell carcinoma of the skin or in situ carcinoma of the cervix uteri (patients adequately treated for other malignancies and without tumor during the last 5 years are eligible).
2. Known cerebral metastasis.
3. Uncontrolled severe infections.
4. Patients with Kaposi’s sarcoma
5. Peripheral neuropathy exceeding CTCAE (Common Terminology Criteria for Adverse Events) v5.0 grade 2.
6. Previous treatment with taxane.
7. Patients with known allergy or severe hypersensitivity to any of the trial drugs or any of the trial drug excipients
8. Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment.
9. Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial.
10. Participation in another clinical trial within 14 days prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Efficacy objective:
*ORR (according to RECIST 1.1 criteria) defined as the percentage of patients with Complete Response (CR) or Partial Response (PR). Patients who discontinue treatment without a tumour assessment will be considered non-responders for the analysis
*PFS defined as the time from the date of randomisation to date of disease progression (radiological or clinical) or death from any cause, whichever occurs first. Patients without tumour progression or death at the time of analysis will be censored at the date of their last tumour assessment.
*4m-DCR is defined as proportion of patients with CR, PR, or a stable disease (SD), 4 months after treatment initiation.
- Value of biomarkers (Ca 19-9, CEA, Lymphocyte to Neutrophil ratio, albumin, Glasgow prognostic score) will be described by absolute or relative variation from baseline. To assess their prognostic or predictive values, baseline values of these biomarkers will be tested using Cox or logistic regression models.
- Dose intensity of chemotherapy will be calculated from doses actually given instead of from targeted doses. Ratio between dose received compared to theoretical ones will be calculated by patient and presented as a percentage.
- Safety and tolerability of treatment (NCI-CTCAE version 5.0) determined through the incidence of adverse events, treatment related adverse events, serious adverse Events (SAE), and death.
- Quality of life (EORTC QLQ-C30) during treatment. A deterioration of scores for five-targeted dimensions: pain, physical and emotional functioning, fatigue, and appetite will be compared between the two treatment arms, while other dimensions will be regarded as exploratory. 5 point deterioration in HRQoL scores will be considered as the minimal clinically important difference (MCID).
- Rate of subsequent chemotherapy (after progression). The type and the date of beginning of first-cycle of each line will be collected.
- Translational research to identify biomarkers predictive of response in this clinical context |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life
Biomarkers study |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
gemcitabine + paclitaxel vs gemcitabine alone |
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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 | 24 |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |