| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Locally advanced adenocarcinoma of pancreas |
| Adénocarcinome localement avancé du pancréas |
|
| E.1.1.1 | Medical condition in easily understood language |
| Pancreas cancer |
| Cancer du pancréas |
|
| 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 | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033600 |
| E.1.2 | Term | Pancreatic adenocarcinoma non-resectable |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
For chemotherapy sequence:
To evaluate the efficacy of the Gembrax/folfirinox chemotherapy sequence
For Radiation Therapy:
To evaluate the feasibility in terms of safety of LInac MRI radiotherapy (RT) in non-progressive patients after chemotherapy sequence |
|
| E.2.2 | Secondary objectives of the trial |
For chemotherapy sequence:
-To evaluate the tolerance of the chemotherapy sequence
For radiotherapy :
- To assess acute toxicity of radiotherapy
- To evaluate dosimetric results
- To correlate dosimetry results to tolerance and survival
For the entire treatment (chemotherapy + radiotherapy)
- To assess progression-free survival
- To assess overall survival
- To evaluate the tolerance of the entire treatment (Tox max)
- To assess late toxicity
- To evaluate the resection rate
- To evaluate the evolution of the turnover marker 19.9
- To assess Quality of Life
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Patient between 18 and 75 years of age on the date of signing the consent form.
2.Histologically or cytologically proven pancreatic adenocarcinoma.
3.Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
4.Non-resecurability criteria, according to NCCN 1.2015 recommendations validated during the centralized proofreading.
5.Non-metastatic patient confirmed by TAP scan and hepatic MRI.
6.Feasibility of MRI-guided radiotherapy confirmed by central review.
7.Uracilemia < 16 ng/ml.
8.Hematologic workup obtained within 14 days prior to inclusion defined by:
-Neutrophils ≥ 1 500/mm3 (1.5 × 109/L);
-Platelets ≥ 100,000/mm3 (100 × 109/L);
-Haemoglobin ≥ 9 g/dl
9.Liver function (obtained within 14 days prior to inclusion) defined by :
-AST and ALT ≤ 2.5 x Upper Limit of the Standard (ULN);
-Total bilirubin ≤ 1.5 x ULN; Patients with a metallic biliary prosthesis due to biliary obstruction from cancer may be included provided that a CT scan with contrast injection and fine cuts to the pancreas has been performed prior to the insertion of the biliary prosthesis, the bilirubin level after insertion of the prosthesis decreases to ≤ 20 mg/L (≤ 34 μmol/l), and in the absence of angiocholitis.
10.Creatinine within the limits of the norm or calculated clearance ≥ 50ml/min for patients with a creatinine value above or below the values of the norm (clearance calculated by the CKD-EPI formula).
11.Calcaemia ≥ LIN and ≤ 1.2 x ULN; magnesia ≥ LIN and ≤ 1.2 x ULN; kalaemia ≥ LIN and ≤ 1.2 x ULN.
12.CA 19.9 < 190 IU/mL (no icteric cholestasis). If CA 19.9 between 190 IU/mL and 500 IU/mL, the patient may be included if PET scan and peritoneal MRI do not reveal any distant metastasis indicating metastasis. If CA 19.9 ≥ 500 IU/ML the patient is non-included.
13.If the patient is sexually active, the patient must agree to use contraception deemed adequate and appropriate by the investigator during the entire period of study drug administration and up to 3 months after discontinuation of treatment. In addition, male and female patients should use a method of contraception after the end of treatment as recommended in the Summary of Product Characteristics or the prescribing information for the product provided in the study manual.
14.Signature of consent prior to any study-specific procedure.
15.Affiliated with a French health insurance plan.
|
|
| E.4 | Principal exclusion criteria |
1.Any previous treatment for pancreatic cancer (chemotherapy, radiation therapy, surgery, targeted therapy or experimental therapy...)
2.Gilbert's syndrome known or homozygous for UGT1A1*28 validated
3.Other concomitant cancer or a history of cancer, with the exception of treated cervical cancer in situ, basal cell or squamous cell skin carcinoma, superficial bladder tumour (Ta, Tis, and T1) or a good prognosis tumour treated curatively without chemotherapy and without evidence of disease within 3 years prior to inclusion.
4.History of radiotherapy with predictable overlap with the radiotherapy treatment under study (history of abdominal irradiation).
5.Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction within the last 6 months.
6.Peripheral neuropathy ≥ grade 2.
7.ECG with a QTc interval greater than 450 ms for males and greater than 470 ms for females.
8.Contraindication to MRI and MRI-guided radiation therapy.
9.History of chronic inflammatory disease of the colon or rectum.
10.Any other serious concomitant uncontrolled disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, kidney, lung, metabolic, or psychiatric disorders).
11.Intolerance or allergy to one of the study drugs (gemcitabine, Abraxane®, oxaliplatin, irinotecan, 5-FU) or to an excipient of one of the drugs (example: fructose) described in the Contraindications or Warnings and Special Precautions sections of the SPC or Prescribing Information.
12.Legal incapacity (patient under curatorship or guardianship).
13.Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion.
14.Patients using VKA (Coumadin...) (possible modification of treatment before inclusion).
15.Uncontrolled active bacterial or viral or fungal infection requiring systemic treatment.
16.Previous or known HIV infection.
17.History of peripheral arterial disease (e.g., claudication, Leo Buerger's disease).
18.Patient who received live attenuated vaccine within 10 days prior to inclusion.
19.Patients with a history of pulmonary fibrosis or interstitial pneumonia.
20.Inability to undergo medical follow-up of the trial for geographical, social or psychological reasons.
21.Participation in another clinical study with an investigational product within the last 30 days prior to inclusion.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
For chemotherapy Sequence:
-Non-progression rate at 4 months according to the RECIST 1.1 criteria.
For radiotherapy:
-Rate of acute digestive non-toxicity in the 90 days of grade 3 or 4 evaluated by the NCI CTC AE v5.0 classification |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Non-progression rate evaluated at 4 months
-Rate of grade 3-4 acute digestive non-toxicity evaluated at 90 days |
|
| E.5.2 | Secondary end point(s) |
For chemotherapy Sequence:
-Tolerance of the chemotherapy sequence as assessed by the NCI CTC AE v5.0 classification.
For radiotherapy :
- Tolerance (acute and late toxicities) of the radiotherapy sequence as assessed by NCI CTC AE v5.0.
- Collection of dosimetric results obtained in terms of dose/volume on predictive dosimetry (coverage of VTP by the prescription dose on totalized dosimetry, dose received at the VWG...)
- Collection and somation of the dosimetric results obtained in terms of dose/volume for adaptive radiotherapy sessions and comparison with predictive dosimetry
- Correlation of dose to organs at risk (duodenum, small intestine, stomach, colon) to the occurrence of digestive toxicities (predictive and adaptive dosimetry)
- Correlation of VTP coverage and VWG dose to progression-free survival and overall survival (predictive and adaptive dosimetry)
For the entire therapeutic sequence (chemotherapy Sequence + radiotherapy)
- Progression-free survival defined as the period of time between the inclusion date and the date of the 1st documented progression or the date of death from any cause.
- Global survival defined as the time between the inclusion date and the date of death from all causes.
- Overall Treatment Tolerance as assessed by NCI CTC AE v5.0 classification.
- Resection rate defined as the percentage of patients operated on during treatment and up to 6 months post-radiation therapy.
- Assess the prognostic impact of the evolution of CA 19.9 on survival
- Quality of Life scores assessed by the EORTC QLQ-C30 and QLQ-PAN26 questionnaires at baseline, 2 months (at the end of Cycle 1), 4 months (at the end of Cycle 2), and at follow-up every 6 weeks after RT.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
-At the end of chemotherapy sequence
-At the end of radiotherapy |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 4 |
| 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 | 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
|
|
| 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
