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

Sponsor

Centre Francois Baclesse, Luxembourg (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03199144

Collaborator

(none)

Enrollment

Location

Arm

46.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Neoplasms	Drug: Chemotherapy Radiation: Stereotactic radiotherapy Procedure: Surgery	Phase 2

Detailed Description

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.
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.

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 :

Clinical exam every 3 months for 3 years
Thoraco-abdominal CT scan at 6, 12, 18, 24, 30 and 36months
PET Scanner at 6, 12, 18, 24, 30 and 36months
CA 19.9 every 3 months for 3 years

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Chemotherapy and Stereotactic Radiosurgery to Pancreatectomy for Borderline Resectable Pancreatic Cancer : Phase II Study

Actual Study Start Date :

Apr 20, 2017

Actual Primary Completion Date :

Mar 19, 2021

Actual Study Completion Date :

Mar 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stereotactic radiotherapy Stereotactic radiotherapy delivering 30 Gy in 5 fractions over 9 days	Drug: Chemotherapy 3 cycles of Gemzar-Abraxane Radiation: Stereotactic radiotherapy Stereotactic radiation treatment delivering 30 Gy in 5 fractions over 9 days Procedure: Surgery Whipple procedure will be the recommended procedure but will be modified according to the initial tumor location

Arm

Intervention/Treatment

Experimental: Stereotactic radiotherapy

Stereotactic radiotherapy delivering 30 Gy in 5 fractions over 9 days

Drug: Chemotherapy

3 cycles of Gemzar-Abraxane

Radiation: Stereotactic radiotherapy

Stereotactic radiation treatment delivering 30 Gy in 5 fractions over 9 days

Procedure: Surgery

Whipple procedure will be the recommended procedure but will be modified according to the initial tumor location

Outcome Measures

Primary Outcome Measures

patient overall survival [follow up during 3 years after patient inclusion]
patient overall survival

Secondary Outcome Measures

positive surgical margins [follow up during 3 years after patient inclusion]
assessment of R1 margin defined according to the British Royal College of pathology
toxicity according the CTCAEv4 [follow up during 3 years after patient inclusion]
toxicity according the CTCAEv4
CA19.9 level post operatively [follow up during 3 years after patient inclusion]
CA19.9 levels post operatively
CEA level post operatively at one month [follow up during 1 month after patient inclusion]
CEA level post operatively at one month

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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