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Neoadjuvant Chemotherapy and Stereotactic Radiosurgery to Pancreatectomy for Patients With Borderline Resectable Pancreatic Cancer

Phase 2
Withdrawn
Conditions
Pancreatic Neoplasms
Interventions
Drug: Chemotherapy
Radiation: Stereotactic radiotherapy
Procedure: Surgery
Registration Number
NCT03199144
Lead Sponsor
Centre Francois Baclesse, Luxembourg
Brief Summary

The goal of the present study is to test if in situations of borderline resectable patients a neoadjuvant treatment combining Gemzar-Abraxane and stereotactic radiosurgery could increase the median OS rates above 30 months that means at least 12 months more than the 18-20 months generally described.

Detailed Description

1. Chemotherapy : 3 cycles of Gemzar-Abraxane. Nab-Paclitaxel will be delivered at day 1 at the dose of 125mg/m2. Gemcitabine will be delivered at the dose of 1g/m2 at days 1, 8 and 15. Three cycles will be given at 4 weeks intervals.

2. PET Scanner and Magnetic resonance Imaging within the 10 days of the third chemotherapy cycle

3.Radiation treatment: Stereotactic radiation treatment delivering 30 Gy in 5 fractions over 9 days, according to the ongoing "CYM 6 Spinal CFB1" which was approved by the "Centre National d'Ethique et de Recherches" (CNER) under the Number 20013/1103 (Ongoing Study 3).

At first, 4 coïl fiducials will be placed inside and/or around the tumor. 10 days later the imaging preparation procedure will be initiated with a CT Scan and MRI simulation. Both exams will be fused using the fiducials. The Clinical Target Volume (CTV) will include systematically the coeliac trunk until the aorta with a margin of at least 1 cm, the origin of the upper mesenteric vessels until the aorta with at least a margin of 1 cm, the space between the Inferior Cava Vein (ICV) and the aorta in front of the pancreatic region, the space between the portal vein and ICV and finally the right lateral border of the ICV in front of the pancreatic region in case of pancreatic head tumors only. The CTV will also include the tumor mass with a 1 cm margin and the locally positive CT scan or PET scanner nodes with a margin of 1 cm provided it does not overlay the digestive structures that will remain after the surgical resection. Finally all these regions will be linked to make a unique CTV structure. The PTV will be defined as an expansion of 5 mm from the CTV. The doses tolerated to the organs at risk figure in the Ongoing Study 3.

Radiation treatment will be initiated 4 weeks after the third chemotherapy cycle.

4. Surgery : Whipple procedure will be the recommended procedure but will be modified according to the initial tumor location. The extension degree of the resection will remain at the discretion of the surgeon. However all the bowel and duodenum irradiated at the prescription dose will be systematically removed whatever the importance of the surgical resection.

Minimal Follow up :

1. Clinical exam every 3 months for 3 years

2. Thoraco-abdominal CT scan at 6, 12, 18, 24, 30 and 36months

3. PET Scanner at 6, 12, 18, 24, 30 and 36months

4. CA 19.9 every 3 months for 3 years

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Biopsy proven pancreatic adenocarcinoma
  • Borderline resectable pancreatic adenocarcinoma (NCCN guidelines)
  • OMS status ≤2
  • Age at presentation >18 y
  • Absolute neutrophil counts >1500/ml
  • Absolute platelet count >100000/ml
  • GOT and GPT <2.5 x the upper limit of normal
  • Total bilirubin < the upper limit of normal
  • Serum creatinin < upper limit of normal
  • Coagulation test within limit of normal (Prothrombin time, INR) +/- 15%
  • No evidence of jaundice at enrolment. If stent required to alleviate jaundice it should be metallic
  • Patient must be able to eat without a feeding tube and can take medications orally
  • Disease must be encompassed in a reasonable radiation field
  • Signed informed consent
Exclusion Criteria
  • Distant metastases
  • Evolutive disease after the neoadjuvant chemotherapy course according RECIST criteria
  • Neuroendocrine tumors
  • Peritoneal dissemination visualized at diagnostic abdominal CT scan
  • Pathologic abdominal nodes visualized at diagnostic abdominal CT scan outside the pancreatic area
  • Pathologic PET scan outside the pancreatic area
  • Inoperability for medical reasons
  • Inability to tolerate chemotherapy for medical (in particular grade II or more neuropathy) or allergic purposes, or for OMS score >2
  • Inability to tolerate Whipple resection
  • Collagenose diseases
  • Cancer evolution outside the pancreatic bed at the PET scanner performed just after the 3 neo adjuvant chemotherapy cycles
  • Any previous cancer in the 5 years excepted a basal skin cell carcinoma or in situ cervical cancer
  • Active infection with HIV, Hepatitis B or c
  • Pregnant patient

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Stereotactic radiotherapyChemotherapyStereotactic radiotherapy delivering 30 Gy in 5 fractions over 9 days
Stereotactic radiotherapyStereotactic radiotherapyStereotactic radiotherapy delivering 30 Gy in 5 fractions over 9 days
Stereotactic radiotherapySurgeryStereotactic radiotherapy delivering 30 Gy in 5 fractions over 9 days
Primary Outcome Measures
NameTimeMethod
patient overall survivalfollow up during 3 years after patient inclusion

patient overall survival

Secondary Outcome Measures
NameTimeMethod
positive surgical marginsfollow up during 3 years after patient inclusion

assessment of R1 margin defined according to the British Royal College of pathology

toxicity according the CTCAEv4follow up during 3 years after patient inclusion

toxicity according the CTCAEv4

CEA level post operatively at one monthfollow up during 1 month after patient inclusion

CEA level post operatively at one month

CA19.9 level post operativelyfollow up during 3 years after patient inclusion

CA19.9 levels post operatively

Trial Locations

Locations (1)

Centre Francois Baclesse

🇱🇺

Esch-sur-Alzette, SUD, Luxembourg

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