| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non resectable locally advanced or metastatic pancreatic cancer |
| Cancer du pancréas localement avancé et non résécable ou métastatique. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non resectable locally advanced or metastatic pancreatic cancer |
| Cancer du pancréas non résécable localement avancé ou métastatique |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033610 |
| E.1.2 | Term | Pancreatic carcinoma metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
•Survival rate every 24W (weeks)
•Tumour assessment: every 8W
-Overall Progression Free Survival (PFS) central and local
-PFS rate
-Time To Progression (TTP) central and local
-TTP rate central and local
-Overall TTP (RECIST 1.1)
-TTP rate (RECIST 1.1)
-Overall Time to Treatment switch (TTS)
-TTS rate
-Best response along study: Complete response (CR) rate, Partial Response (PR) rate, Progressive disease (PD)
-Level of serum CA 19-9
•Quality of life assessment: every 4W until W48 then every 8W
-EORTC QLQ-C30 questionnaire
-ECOG Performance Status
-Patient’s visual analogue scale (VAS) and Brief Pain Inventory (BPI)
-Analgesic consumption
•Pharmacogenomic assessment
Relationship between genomic data and all efficacy variables
•Safety profile (NCI CTC v4.02 classification)
-Discontinuation for related AE
-Related Grade 3 non haematological or any related grade 4 related AE
-AE leading to death
-Cardiac AE
-AE related to cancer pain |
|
| 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 |
| Pharmacogenomic (DNA) and management of potential risk analysis |
|
| E.3 | Principal inclusion criteria |
First randomisation inclusion criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas, non resectable
2. Patient with pain related to the disease, as assessed by the investigator and the patient:
- Pain related to the disease as assessed by the investigator is defined as clinical and documented evaluation by the investigator during physical examinations at screening and/or baseline.
- Pain, as assessed by the patient is defined as at least one value out of two values > 20mm on Visual Analogic Scale at screening or baseline. Visual Analogic scale consists in the visual representation of pain amplitude as perceived by the patient. The amplitude is represented by a 100 mm long line having no reference marks. One extremity indicates an absence of pain (0 value) and the other the worst imaginable pain (100 value).
OR
Patient treated with opioid analgesics at a dose ≥ 1 mg/kg/day (morphinic equivalent).
OR
Patients with ‘genetic fingerprint of aggressiveness’: ACOX1 (DCt ≤ 3.05)’
3. Chemotherapy naïve patient for the advanced/metastatic disease
4. Documented decision justifying non eligibility for surgical resection.
5. Patient with measurable tumor lesions with longest diameter ≥ 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according to RECIST 1.1
6. Patient with ECOG ≤ 1
7. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 75 x 109/L
• AST/ALT ≤ 5 x ULN
• Gamma GT ≤ 5 x ULN
• Bilirubin ≤ 3 x ULN
• Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1x LLN
• Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
• Patient with life expectancy > 3 months
8. Male or female patient, age 18 years
9. Patient with a BMI > 18 kg/m² and >40 kg
10. Male patient and female patient of childbearing potential must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception (with failure rate < 1%) during the study and for 3 months after the last treatment intake for women
11. Female patient of childbearing potential must agree to have a negative pregnancy test at screening and baseline.
12. Patient able and willing to comply with study procedures as per protocol
13. Patient able to understand the patient card and to follow the patient card procedures, in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity during the first 2 months of treatment.
14. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent.
Second randomisation inclusion criteria:
1. Patient under disease progression (according to RECIST 1.1 or investigator claim) after first line treatment with masitinib in combination with gemcitabine
OR
Patient not under disease progression but who discontinued First line treatment for any adverse event not defined as a severe adverse event (grade ≥ 3) due to the mechanism of action of masitinib (i.e. rash, nausea, vomiting or diarrhea).
2. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 9 g/dL
• Platelets (PTL) ≥ 75 x 109/L
• AST/ALT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastases)
• Gamma GT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
• Bilirubin ≤ 1.5 x ULN (≤ 3xULN in case of liver metastases)
• Normal Creatinine or if abnormal creatinine, creatinine clearance ≥ 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1x LLN
• Urea < 2 x ULN
Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is ≥ 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
15. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. |
|
| E.4 | Principal exclusion criteria |
First randomisation exclusion criteria:
1. Patient treated for a cancer other than pancreatic cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
2. Patient with no pain related to the disease (as defined in the inclusion criterion number 2) and no genetic fingerprint of aggressiveness
3. Patient with ECOG ≥ 2
4. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension according to the judgement of the investigator, or symptomatic hypertension
6. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
7. Pregnant, intent to be pregnant, or nursing female patient
Second randomisation exclusion criteria:
1. Patient intolerant to masitinib
The patient is considered as intolerant to masitinib if he/she presented with a severe adverse event (grade ≥ 3) due to the mechanism of action of masitinib (i.e. rash, nausea, vomiting or diarrhea) which led to interruption and/or dose reduction of first line treatment followed by a re-challenge of first line treatment leading to the same severe adverse event.
2. Patient having presented with disabling or life-threatening adverse event due to first line treatment
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Overall Survival (OS) is defined as the time from the randomization to the date of documented death |
| - Survie globale |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Date of documented death |
| Date du décès documenté |
|
| E.5.2 | Secondary end point(s) |
| Progression Free Survival |
| Survie globale sans progression |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Every 8 weeks |
| Chaque 8 semaines |
|
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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 | Yes |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Austria |
| Belgium |
| Brazil |
| Canada |
| China |
| Czech Republic |
| Greece |
| Hong Kong |
| Hungary |
| India |
| Italy |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Morocco |
| Peru |
| Philippines |
| Poland |
| Romania |
| Russian Federation |
| Singapore |
| South Africa |
| Spain |
| Tunisia |
| Ukraine |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| Patient treated until disease progression limiting toxicity or consent withdrawal. Follow-up performed until patient's death |
|
| 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 | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
Print
