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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Drug: Chemotherapy; Radiation: Stereotactic radiotherapy; Procedure: Surgery

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

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Luxembourg
  • SUD
    • Esch-sur-Alzette, SUD, Luxembourg, L-4240
      • Centre Francois Baclesse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patient overall survival	patient overall survival	follow up during 3 years after patient inclusion

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Francois Baclesse, Luxembourg

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 20, 2017
• Primary Completion (ACTUAL): March 19, 2021
• Study Completion (ACTUAL): March 19, 2021

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (ACTUAL): June 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 23, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Chemotherapy; Pancreatic Neoplasms; Neoadjuvant treatment; Borderline resectable; Stereotactic radiation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: Pancreas cancer neoadjuvant

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No