E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with resectable or borderline resectable pancreatic cancer. |
patienten met een operabel of borderline operabel pancreas carcinoom
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E.1.1.1 | Medical condition in easily understood language |
patients with resectable or possible resectable pancreatic cancer. |
Patienten met een operabel of mogelijk operabel kankergezwel van de alvleesklier |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether the addition of preoperative radiochemotherapy to the standard treatment, consisting of explorative laparotomy, pancreaticoduodenectomy if possible, followed by adjuvant chemotherapy, improves the overall survival (analyzed by intent to treat) of patients with resectable or borderline resectable pancreatic cancer. |
Het onderzoeken of preoperative radiochemotherapie voorafgaande aan de standaard behandeling, bestaande uit exploratieve laparotomie gevolgd door pancraticoduodenectomie indien mogelijk, en adjuvante chemotherapie, de overall survival verbetert (geanalyseerd door intent to treat) van patienten met een operabel of borderline operabel pancreas carcinoom
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E.2.2 | Secondary objectives of the trial |
to compare between the study arms
- the resection rate
- the microscopically complete (R0) resection rate
- the disease free survival
- the time to locoregional failure
- the time to distant metastases
- the postoperative complications and morbidity
To assess in experimental arm
- the radiological response rates after preoperative radiochemotherapy (RECIST criteria)
- the pathological response rates after preoperative radiochemotherapy
- the toxicity of preoprative radiochemotherapy according to Common Terminology Criteria of Adverse Events 4 (CTC-AE-4) |
- de resectie maatstaf wordt gedefinieerd als het percentage van in aanmerking voor randomisatie komende patienten die daadwerkelijk een resectie ondergaan. Patienten die helemaal geen exploratieve laparotomie ondergaan of een exploratieve laparotomie maar geen resectie worden beschouwd als een mislukking.
- RO resectie maatstaf wordt gedefinieerd als het percentage van in aanmerking komende patienten die een microscopisch complete (of RO) rescetie ondergaan. .
- Ziektevrij overleven wordt gedefinieerd als overleven zonder duidelijk terugkerende alvleesklierkanker vanaf de datum van randomisatie, - Postoperatieve complicaties worden gedefinieerd volgens de internationaal geaccepteerde Clavien-Dindo classificatie en definities van post-operatieve complicaties na pancreas chirurgie (pancreas fistels, vertraagde ontlediging van de maag, bloeding) door de Internationale SGPC (analyse van intent-to-treeat en per-protocol by patienten dioe PD/Whipple ondergaan) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologicallyconfirmed adenocarcinoma of the pancreas
2. Primarilly resectable tumours or Borderline resectable tumours
3. Karnofsky performance status ≥ 70%
4. Ability to undergo surgery and radiochemotherapy
5. Leucocytes ≥ 3.5 X 10.9/l
6. Platelets ≥ 100X 10.9/l
7. Hemoglobin ≥ 6 mmol/l
8. renal function: E-GFR > 50 ml/min
9. Age ≥ 18 jaar
10.Written informed concent
11. Patients with reproductive potential must use effective contraception |
1. Histologisch of cytologische bevestigde adenocarcinoom van de pancreas
2. Primair verwijderbare tumor of Borderline verwijderbare tumor
3. Karnofsky performance status ≥ 70%
4. Geschiktheid om operatie en chemotherapie te ondergaan
5. Leucocytes ≥ 3.5 X 10.9/l
6. Platelets ≥ 100X 10.9/l
7. Hemoglobine ≥ 6 mmol/l
8. Nierfunctie: E-GFR > 50 ml/min
9. Leeftijd ≥ 18 jaar
10.Ondertekend instemmingsformulier
11. Patienten in de vruchtbare leeftijd moeten effectieve contraceptie gebruiken |
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E.4 | Principal exclusion criteria |
1.T1 resectable tumours, centrally located with no connection to the SMA, Celiac axis, CHA or SMV/PV
2. Claerly locally advanced, irresectable, tumours
3. Carcinoma of the Papilla Vateri
4. Co morbidity precluding surgery or radiochemotherapy
5. Distant metastases, including cytologically prove N2 lymph node metastases (base of the celiac trunk or between inferior vena cava and aorta)
6. Previous treatment of pancreatic cancer (i.e. radiotherapy or chemotherapy)
7. Pregnancy
8. Imminent bowel obstruction
9. Active bleeding
10 Uncontrolled infection
11 Anamnestically known positive status for HIV or hepatitis B or C |
1.T1 operabele tumoren, centraal gelegen met geen verbinding met de SMA, Coeliakie as, CHA of SMV / PV
2. lokaal operabele, tumoren
3. Carcinoom van de papil Vateri
4. Co morbiditeit die zich verzetten tegen een operatie of radiochemotherapie
5. Metastasen op afstand, met inbegrip van cytologisch bewijzen N2 lymfeklier metastasen (basis van de coeliakie stam of tussen de onderste holle ader en de aorta)
6. Eerdere behandeling van pancreaskanker (dat wil zeggen radiotherapie of chemotherapie)
7. zwangerschap
8. Dreigende darmobstructie
9. actieve bloeding
10 Ongecontroleerde infectie
11 anamnese bekende positieve status voor HIV of hepatitis B of C |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall survival is defined as the period of time between randomization and death from any cause. Patients alive at last follow-up are censored. |
Algehele overleving deze wordt gedefinieerd tussen de periode van randomisatie en overlijden ongeacht de oorzaak. Patiënten die in leven zijn tijdens de laatste follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One of the interim analysis is planned after 100 patients have been followed until death or for at least 12 months after inclusion.
All cause actuarial survival curves in the two randomization groups will be compared by intent to treat The log rank test statistics will be used to compare the Kaplan-Meier survical curves of two randomization groups |
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E.5.2 | Secondary end point(s) |
- Resection rate is defined as the percentage of eligible randomized patients that actually underwent a resection. Patients that do not undergo an explorative laparotomy at all or do undergo an explorative laparotomy but not a resection are considered a failure.
- R0 resection rate is defined as the percentage of eligible randomized patients that underwent a microscopically complete (or R0) resection. The resection is considered R0 if the inked margin is further than 1 mm distinct from any tumour cells.
- Disease free survival is defined as survival without overt recurrent pancreatic cancer from the date of randomization, as discovered following complaints of the patient or on routine CT-scan at 6 months intervals. Any sign of recurrent or persistent disease, locoregional or distant, as well as death from any cause is considered an event for this endpoint. Patients that do not undergo an explorative laparotomy at all or do undergo an explorative laparotomy but not a resection are considered a failure at time point zero.
- Time to locoregional failure is defined as the period of time without locoregional recurrence after randomisation. Locoregional recurrence is considered an event and patients are censored at death or distant metastases without locoregional recurrence. Patients that do not undergo an explorative laparotomy at all or do undergo an explorative laparotomy but not a resection are considered a failure at time point zero.
- Time to distant metastases is defined as the period of time without distant metastases after randomisation. Distant metastases are considered an event and patients are censored at death.
- Postoperative complications are defined according to the internationally-accepted Clavien-Dindo classification and definitions of post-pancreatic surgery complications (pancreatic fistula, delayed gastric emptying, bleeding) by the International Study Group on Pancreatic Surgery (analysis on intent-to-treat and per-protocol in patients undergoing PD/Whipple). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
One of the interim analysis is planned after 100 patients have been followed until death or for at least 12 months after inclusion.
All cause actuarial survival curves in the two randomization groups will be compared by intent to treat The log rank test statistics will be used to compare the Kaplan-Meier survical curves of two randomization groups |
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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 | No |
E.6.5 | Efficacy | No |
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 | 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 |
compared with standard procedure chemotherapy (Gemzar) after surgery |
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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 | 14 |
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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36 months and 12 months after the last patient has been entered |
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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 | 12 |
E.8.9.1 | In the Member State concerned days | |