None listed
Conditions
Brief summary
Update The aim of this study is to assess the benefit of adding high precision radiotherapy to chemotherapy and surgery for the treatment of pancreatic cancer. Who is it for? You may be eligible for this study if you are aged 18 to 75 years old, have pancreatic cancer and have adequate liver function. You must not have received prior treatment for your pancreatic cancer. Study details Participants will be randomised by chance into two groups. Both of the groups will undergo a chemotherapy regimen which includes either one of the following drug combinations; 1) mFOLFIRINOX or 2) Gemcitabine/Nab-paclitaxel. One of the groups will have additional high precision radiotherapy called stereotactic radiotherapy. After this treatment, you may go on to have surgery.. Whether or not you have surgery, the treating team will then have a discussion with participants about further treatment with chemotherapy. All participants will complete a number of questionnaires, consent to their biopsies and resected tissue being analysed in a laboratory. Participants will be followed up for up to 4 years. This research may demonstrate that the addition of high precision radiotherapy to pancreatic cancer treatment improves patient outcomes and reduces the rates of cancer recurrence.
Interventions
Arm B: Patients will commence with initial chemotherapy* for 12 weeks followed by SBRT** (intervention arm) prior to consideration of surgical resection.
Following restaging, resectable patients will proceed to surgery followed by adjuvant chemotherapy with mFOLFIRINOX as per Option 1 below or gemcitabine/capecitabine***
Those not suitable for resection due to disease being unresectable (PR, SD) or for medical reasons should continue with mFOLFIRINOX as per Option 1 below OR gemcitabine + nab-
Arm B: Patients will commence with initial chemotherapy* for 12 weeks followed by SBRT** (intervention arm) prior to consideration of surgical resection. Following restaging, resectable patients will proceed to surgery followed by adjuvant chemotherapy with mFOLFIRINOX as per Option 1 below or gemcitabine/capecitabine*** Those not suitable for resection due to disease being unresectable (PR, SD) or for medical reasons should continue with mFOLFIRINOX as per Option 1 below OR gemcitabine + nab-paclitaxel. *Options for Initial Chemotherapy: Option 1: (Preferred) mFOLFIRINOX (6 cycles) 6 x 14 day cycles of oxaliplatin (85mg/m2 IV), irinotecan (150mg/ m2), 5-fluorouracil (2400mg/m2 CIV), leucovorin (50mg IV bolus) Option 2: Gemcitabine + nab-paclitaxel (3 cycles) 3 x 28 day cycles of gemcitabine and nab-Paclitaxel Gemcitabine (1000mg/m2 IV) and nab-Paclitaxel (125mg/m2 IVI) day 1, day 8 and day 15 of 28 day cycle **Arm B patients, intervention: Radiation: Stereotactic Radiotherapy (SBRT) 40 Gray (Gy) in 5 fractions over two weeks, 8 Gy per fraction. Maximum of four treatments per week, with two consecutive days permitted but not three. ***Adjuvant Chemotherapy: 3 x cycles of 1000 mg/m2 gemcitabine administered once a week for three of every 4 weeks (one cycle) with 830 mg/m2 oral capecitabine administered for 21 days followed by 7 days rest (one cycle).
Sponsors
Australasian Gastro-Intestinal Trials Groups (AGITG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
*Adults, aged between 18-75 years, with pathologic confirmation of pancreatic adenocarcinoma *Patients who are treatment-naïve, or have been commenced on chemotherapy less than or equal to 28 days prior to randomisation. *Any of the following: T3 (tumour greater than 4 cm), Extrapancreatic extension, Node positive , Borderline resectable pancreatic cancer, locally advanced pancreatic cancer *Measurable disease according to RECIST v1.1 *ECOG performance status 0-1 *Adequate renal and haematological function *Adequate hepatic function. Defined as bilirubin less than 1.5 X ULN (Upper Limit of Normal), AST + ALT less than 3.0 X ULN. If a patient was recently stented with improving bilirubin, the patient can be randomised with bilirubin up to 3 x ULN provided chemotherapy is not administered until within the stated thresholds. *Study treatment planned to start within 14 days of randomisation *Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments *Signed, written informed consent
Exclusion criteria
. Tumour size greater than 70mm . Duodenal infiltration seen on endoscopy . Prior abdominal radiotherapy,or previous radiation where the 5 Gy isodose line crosses into the treatment field (or an approximation of this if axial based imaging not utilised). . Evidence of metastatic disease on baseline radiologic investigations . History of another malignancy within 2 years prior to randomisation, except adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, -superficial transitional cell carcinoma of the bladder, any Stage 1 endometrial carcinoma, low risk prostate cancer with PSA less than or equal to 10 and Gleason score of less than or equal to 6 treated with any modality, including active surveillance-Patients with treated early-stage breast cancer on adjuvant endocrine therapy are eligible provided they have been disease free for at least 2 years after definitive treatment. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive treatment. . Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety . Neuroendocrine pancreatic carcinoma . Life expectancy of less than 3 months . Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to randomisation. Men must use a reliable means of contraception . Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
Outcome results
None listed