| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| 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 |
To assess the efficacy of FOLFOX in comparison to gemcitabine in metastatic first-line in patients with pancreatic adenocarcinoma and non-fit for FOLFIRINOX.
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| E.2.2 | Secondary objectives of the trial |
he others efficacy parameters centered on the tumor: objective response rate and disease control rate (RECIST v1.1, in case of evaluable lesion), duration of response, duration of disease control
- The progression free survival (PFS)
- The evolution of biomarkers Ca 19-9 and CEA to assess their prognostic value at inclusion and their predictive value under treatment
- The toxicities according to International Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- The safety of both arms
- The quality of life
- The dose intensity (DI) of each protocol
- The Quality-Adjusted Survival
- The rate and type of second-line / third-line regimens chemotherapy
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,
4. Metastatic disease confirmed (stage IV),
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),
6. Age ≥18 years,
7. Patient non-fit for FOLFIRINOX, with ECOG performance status (PS) 0-2
8. For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required. An albumin infusion is not permitted before the inclusion test,
9. Haematological status: neutrophils (ANC) >1.5x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,
10. Adequate renal function: serum creatinine level <150μM,
11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
12. Total bilirubin ≤3 x ULN,
13. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
14. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
15. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment,
16. Affiliation to a French social security system (recipient or assign).
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| E.4 | Principal exclusion criteria |
1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
2. Local or locally advanced disease (stage I to III),
3. Patient uses warfarin,
4. Patient receiving concomitant radiotherapy,
5. Uncontrolled hypercalcemia,
6. Pre-existing permanent neuropathy (NCI grade ≥2),
7. Poor nutritional status
8. Known dihydropyrimidine dehydrogenase (DPD) deficiency,
9. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
10. Treatment with any other investigational medicinal product within 28 days prior to study entry,
11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,
13. Known uncontrolled bacterial infection
14. History or active interstitial lung disease (ILD),
15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
16. Patients with known allergy to active substance or any excipient of study drugs,
17. Allergy to iodinated contrast product
18. Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine and concomitant administration of prophylactic phenytoin
19. Patients under legal protection or unable to consent
20. Participation in another interventional research
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival (OS) at 24 months |
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| E.5.2 | Secondary end point(s) |
Objective response rate and disease control rate (RECIST criteria 1.1), duration of response, duration of disease control.
- Progression-free survival (PFS) will be defined as the delay between the date of inclusion and the date of the first event (progression or death) or date of last news if the patient is alive without any progression.
- Ca 19-9 and CEA levels, at inclusion and their dynamic change under treatment.
- Toxicities will be described by type of toxicities and grades according to International Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Safety: rate of serious adverse events, grade 3-4 toxicities (hematologic and non-hematologic). Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
- Quality of life will be studied by means of the EORTC QLQ C-30 questionnaire, the health-related quality of life (HRQoL) and
the consensual geriatric minimum data set (SOFOG) for patients ≥75 years and
- The dose-intensity (DI) of each protocol will be calculated based on the number of cycles received by each patient. The relative DI will be calculated as the ratio of the DI to the DI indicated in the protocol (obtained as the dose specified per cycle in mg/m²).
- The Quality-adjusted Time WIthout Symptoms of disease or Toxicity (Q-TWIST)
- Type of second-line and third-line regimens and the date of beginning of first-cycle of each line will be collected.
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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 | No |
| 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) | 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 | 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 | 43 |
| 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 | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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