None listed
Conditions
Brief summary
This study will determine the effect of stereotactic ablative body radiotherapy (SBRT) with endoscopic ultrasound inserted fiducial markers for unresectable pancreatic cancer. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have adenocarcinoma of the pancreas which has been deemed inoperable and are planning for treatment with combined chemotherapy. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive chemotherapy only In this trial, patients receive a FOLFIRINOX based regime given over a 4 month period (oxaliplatin, irinotecan, leucovorin, fluorouracil every 2 weeks, totalling 8 cycles). While participants in the other group will receive chemotherapy of Folfirinox based regime and they will also receive 2 weeks of Capecitabine as a radio-sensitizer (850 mg/m2 twice daily for 5 days of each week (Monday to Friday)), prior to fiducial guided SBRT (25Gy in 5 fractions delivered to gross tumour and simultaneous integrated boost of 35Gy in 5 fractions to region of vessel encasement). Participants will be followed-up for up to 12 months post-completion of treatment to determine survival rates, resectability rates, technical success of fiducial placement, pain and quality of life. The use of radiotherapy, either alone or in combined with chemotherapy, has been evaluated in the past but evidence is limited due the lack of ability to deliver the radiation to the pancreatic mass without causing adverse effects to surrounding organs. One of the approaches to overcome this problem is to use marker-guided stereotactic radiotherapy, which is increasingly applied in the field of radiation oncology. The majority of studies have looked at technical success and safety rather than patient survival and quality of life.
Interventions
Stereotactic ablative body radiotherapy for Unresectable Pancreatic cancer with Endoscopic ultrasound inserted fiducial markers and concuRrent chemotherapy (SUPER) trial.
All aspects of this study will be discussed with each patient during the recruitment process. An information sheet will be provided, and each patient will be given the opportunity to discuss this study will a medical practitioner, friends or family prior to involvement. Each participant will give written, informed consent and
Stereotactic ablative body radiotherapy for Unresectable Pancreatic cancer with Endoscopic ultrasound inserted fiducial markers and concuRrent chemotherapy (SUPER) trial. All aspects of this study will be discussed with each patient during the recruitment process. An information sheet will be provided, and each patient will be given the opportunity to discuss this study will a medical practitioner, friends or family prior to involvement. Each participant will give written, informed consent and will be free to withdrawal from the study at any time. This would start to assess the safety and outcome of combined FOLFIRINOX chemotherapy and stereotactic radiotherapy guided by EUS inserted fiducial markers in locally advanced PDAC. If the approach is deemed safe, we will then apply for a further ethics submission to perform a multi-centre, randomized control trial looking at SBRT combined with chemotherapy versus chemotherapy alone. This would involve patients with locally advanced disease, deemed as either unresectable or borderline resectable. In this study, all patients who are deemed to have inoperable pancreatic cancer from assessment of a multi-disciplinary team (combined hepato-biliary surgery, radiation oncology and medical oncology), and planned for treatment with combined chemoradiotherapy will be recruited. Patients receive a FOLFIRINOX based regime given over a 4 month period (oxaliplatin, irinotecan, leucovorin, fluorouracil every 2 weeks, totaling 8 cycles). This is followed by 2 weeks of Capecitabine as a radio-sensitizer (850 mg/m2 twice daily for 5 days of each week (Monday to Friday)), then followed by fiducial guided SBRT (25Gy in 5 fractions delivered to gross tumour and simultaneous integrated boost of 35Gy in 5 fractions to region of vessel encasement). The dose of each of the drugs in the FOLFINIROX based regime will be variable (as determined by treating physician), and mode of administration will be IV. The drugs for the FOLFIRINOX based regime will be given simultaneously. The mode of administration for capecitabine will be oral tablet. Patients to undergo the following tests before treatment: 1. bMRI abdomen and/or whole body PET scan 2. Bilirubin 3. Liver function 4. CA 19.9 and CE 5. Complete blood examination Four gold fiducials will be placed by EUS guidance in 4 quadrants of the pancreatic mass to outline its peripheral borders, using a specifically designed 22G EchoTip Fiducial needle. CT simulation will be performed within 5 days after fiducial placement. Before simulation, patients will commence a low residue diet, fast for 6 hours prior and may require appropriate analgesia depending on level of patient discomfort. Simulation will employ full body immobilization (Omni V SBRT system), multidetector 4DCT with 3mm slices and IV contrast (late arterial phase scan). Patient to be positioned supine with arms raised above the head. Simulation tumour motion study to be assessed to determine the degree of tumour excursion. For target displacement of >5mm, consideration to be given to abdominal compression to address the issue of movement at the oncologists discretion. Scan limits are from nipple to umbilical level. Reference tattoos to be used. The duration of the fiducial placement will be 5 minutes, CT simulation will be for 15 minutes, and fiducial guided SBRT will be for 90 minutes. Treatment planning will require MRI and/or PET fusion to ensure accurate delineation of the target volume on the 4DCT maximum intensity projection. Organ at risk and radiotherapy plan to be generated from the 4DCT average scan. SBRT will be scheduled to commence within 2 weeks. Treatment delivery will be in 5 fractions, with a maximum of 2 fractions per week at least 48 hours apart. Patient to be pretreated with oral dexamethasone 4mg and Ondansetron 8mg, approximately 1 hour prior to treatment. Consideration to be given to pretreatment Paracetamol 1g and Lorazepam 1mg, if the patient is in pain or anxious, respectively. Patients will require the same full body immobilization as determined at time of CT simulation. The linear accelerator will have high definition multileaf collimators and cone beam CT technology available. An onboard image match to be carried out for bone alignment followed by a pretreatment cone beam CT scan. An online image matching process of the gold seed fiducial markers to the reference image will be carried out. Exportation of the duodenal region of interest will aid in online matching. The tolerance for treatment couch shift based on cone beam CT is 0mm and for repeat cone beam CT acquisition this will be 3mm. For biomarker applications, sections of cell-block material from the resected specimens of the patients receiving fiducial guided radiochemotherapy, will be assessed for S100A2 and S100A4 expression using immunohistochemistry. Serum levels or CA 19-9 (Carbohydrate antigen 19-9) and CEA (Carcinoembryonic Antigen) will also be measured.
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas. 2. Locally advanced disease, which is deemed: a) Unresectable; or b) Borderline resectable , which includes these tumour characteristics: (i) - involvement of superior mesenteric or portal vein but with sufficient vessel proximal and distal to the area of vessel involvement (which allows safe resection and reconstruction) (ii) - gastroduodenal artery encasement up to the hepatic artery and involvement of the hepatic artery without extension to the celiac axis (iii) - superior mesenteric artery involvement less than 180 degrees 3. Patients should have a projected life expectancy of at least 6 weeks 4. ECOG performance status less than or equal to 2 5. 18 years old or older 6. Measurable disease as defined by RECIST 1.1. 7. Serum bilirubin less than 30 µmol/L, after successful biliary decompression with stents 8. Adequate bone marrow function, WCC greater than 3 x 10^9/L, platelets greater than100 x 10^9/L 9. Written informed consent 10. Those deemed for combined chemoradiotherapy as per multi-disciplinary team consensus
Exclusion criteria
1. Metastatic disease from pancreatic cancer 2. Prior chemotherapy or radiotherapy 3. History of other malignant diseases other than non-melanomatous skin cancer or in-situ carcinoma of the uterine cervix 4. Clinical evidence of uncontrolled angina pectoris, cardiac failure, clinically significant cardiac arrhythmia, or other serious uncontrolled medical condition 5. Pregnant or lactating (any woman of childbearing potential must have a pregnancy test prior to randomization and must take adequate precautions to prevent pregnancy during treatment) 6. Tumour size greater than 75mm
Outcome results
None listed