Voorbehandeling met bestraling en chemotherapie gevolgd door operatie versus alleen operatie voor operatief verwijderbare of mogelijk verwijderbare alvleesklierkanker. Een gerandomiseerd fase III onderzoek.|
|- candidate number||13732|
|- NTR Number||NTR3709|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||8-nov-2012|
|- Secondary IDs||2010-019225-33 / UVA2012-5696 EUDRACT / KWF datamanagement subsidie|
|- Public Title||Voorbehandeling met bestraling en chemotherapie gevolgd door operatie versus alleen operatie voor operatief verwijderbare of mogelijk verwijderbare alvleesklierkanker. Een gerandomiseerd fase III onderzoek.|
|- Scientific Title||Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: A multicentre randomized phase III clinical trial/|
|- hypothesis||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.|
|- Healt Condition(s) or Problem(s) studied||Resectable pancreatic carcinoma, Borderline resectable pancreatic carcinoma|
|- Inclusion criteria||1. Histologically or cytologically confirmed adenocarcinoma of the pancreas;|
2. Primarily resectable tumours or Borderline resectable tumours (see table 1, p7 and hereunder) (exception, T1 centrally located tumours with no vascular involvement at all);
3. WHO performance status ≤ 1;
4. Ability to undergo surgery and radiochemotherapy;
5. Leucocytes ≥ 3.5 X 109/l;
6. Platelets ≥ 100X 109 /l;
7. Haemoglobin ≥ 6 mmol/l;
8. Renal function: E-GFR > 50 ml/min;
9. Age ≥ 18 years;
10. Written informed consent;
11. Patients with reproductive potential must use effective contraception.
|- Exclusion criteria||1. T1 resectable tumours, centrally located with no connection to the SMA, Celiac axis, CHA or SMV/PV;|
2. Clearly locally advanced, irresectable, tumours (see table 1, p7 and hereabove);
3. Carcinoma of the Papilla Vateri;
4. Co morbidity precluding surgery or radiochemotherapy;
5. Previous radiotherapy or chemotherapy precluding radiochemotherapy;
6. Distant metastases, including cytologically proven N2 lymph node metastases (base of the celiac trunk or between inferior vena cava and aorta);
8. Imminent bowel obstruction;
9. Active bleeding;
10. Uncontrolled infection;
11. Anamnestically known positive status for HIV or hepatitis B or C.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2013|
|- planned closingdate||1-jan-2016|
|- Target number of participants||244|
|- Interventions||Two arm, randomized trial for patients with resectable or borderline resectable pancreatic cancer.
Standard arm: Explorative surgery, if possible resulting in pylorus preserving or classical pancreaticoduodenectomy, followed by standard adjuvant chemotherapy.
Standard adjuvant chemotherapy is Gemcitabine 1000 mg/m2 day 1,8 and 15, one week rest, for six courses.
Experimental arm: Preoperative chemoradiotherapy followed by explorative surgery, if possible resulting in pylorus preserving or classical pancreaticoduodenectomy, followed by the remainder of adjuvant chemotherapy.
Preoperative treatment (experimental arm) is Gemcitabine 1000 mg/m2 day 1,8, one week rest. Then Gemcitabine 1000 mg/m2 day 1,8,15, concomitant with radiotherapy: 36 Gy, 15 fractions of 2.4 Gy. Then Gemcitabine 1000 mg/m2 day 1,8 one week rest.
After surgery (experimental arm) four (remaining) courses of Gemcitabine 1000 mg/m2 day 1,8,15, one week rest. This is to make sure that the total amount of Gemcitabine gifts is barely different in the experimental arm compared to the standard arm.
In the experimental arm, pretreatment evaluation including laparoscopy is necessary, as well as treatment of eventual jaundice. Also post radiochemotherapy evaluation needs to be performed.
|- Primary outcome||Overall survival.|
|- Secondary outcome||To compare between the study arms:|
1. The resection rate;
2. The microscopically complete (R0) resection rate;
3. The disease free survival;
4. The time to locoregional failure;
5. The time to distant metastases;
6. The postoperative complications and morbidity.
To assess in the experimental arm:
1. The radiological response rates after preoperative radiochemotherapy (RECIST criteria);
2. The pathological response rates after preoperative radiochemotherapy;
3. The toxicity of preoperative radiochemotherapy according to Common Terminology Criteria for Adverse Events 4 (CTC-AE 4).
|- Timepoints||Final analysis will take place one year after full inclusion.|
|- Trial web site||www.DPCG.nl|
|- CONTACT FOR PUBLIC QUERIES||Dr. G. Tienhoven, van|
|- CONTACT for SCIENTIFIC QUERIES||Dr. G. Tienhoven, van|
|- Sponsor/Initiator ||Academic Medical Center, Department of radiation oncology |
(Source(s) of Monetary or Material Support)
|- Publications||Van Tienhoven G, Gouma, DJ, Richel DJ. Neoadjuvant chemoradiotherapy has a potential role in pancreatic carcinoma Therapeutic Advances in Medical Oncology, 2011;3:27-33|
|- Brief summary||Pancreatic cancer has a dismal prognosis. Pancreaticoduodenectomy may offer cure but only a small percentage of patients can undergo a resection, and also in this cohort the survival is poor. Adjuvant chemotherapy offers a modest survival improvement [Oettle 2008]. From multiple single arm phase two studies and a SEER database observational study, there is a suggestion that preoperative radiochemotherapy may offer an improvement by increasing the resection rate, increasing the R0 resection rate hence improving overall survival in borderline resectable and resectable pancreatic cancer [Stessin 2008, Gillen 2010, van Tienhoven 2011]. A major difficulty in the interpretation of the literature is that most studies are single arm studies, with a selected group of patients that only report on the subset of patients actually undergoing a resection. This hampers comparison of study results and disables proper analysis of a potential increase in resection rate. The only way to evaluate the role of preoperative radiochemotherapy concerning resection rate, R0 resection rate and thus overall survival is to perform a randomized study, analyzing the results by intent to treat [van Laethem 2011].|
To investigate whether preoperative radiochemotherapy can indeed improve overall survival in resectable and borderline resectable pancreatic cancer, the Dutch Pancreatic Cancer Group initiates a prospective randomized phase III study: PREOPANC.
In the experimental arm, biliary drainage and laparoscopy to rule out small metastases should be performed before the start of radiochemotherapy. A well tested radiochemotherapy schedule, based on three courses of full dose gemcitabine chemotherapy, was adopted [Talamonti 2006, Small 2008,2011].
A total of 244 patients (176 events) are needed to assess a difference of six months in median survival by intent to treat (from 11-17 months).
|- Main changes (audit trail)|
|- RECORD||8-nov-2012 - 1-dec-2012|
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