MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
- Conditions
- Pancreatic Cancer
- Interventions
- Drug: mFOLFIRINOXRadiation: Stereotactic Radiotherapy (SBRT)Procedure: Pancreatoduodenectomy (Whipple procedure)
- Registration Number
- NCT04089150
- Lead Sponsor
- Australasian Gastro-Intestinal Trials Group
- Brief Summary
This is a prospective, multicentre randomised, phase II clinical trial, with randomisation 2:1 by minimisation and stratification by tumour stage, planned chemotherapy and institution.
- Detailed Description
This is a prospective, multicentre randomised, phase II clinical trial to evaluate safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in patients with high-risk and borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). High risk defined as any patient with tumour \>4cm, extrapancreatic extension or node positive disease.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 120
-
Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma
-
Any of the following
- T3 (tumour >4 cm)
- Extrapancreatic extension
- Node positive (stage IIB)
- 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 <1.5 X ULN (Upper Limit of Normal), AST + ALT <3.0 X ULN. In patients who have had a recent biliary drainage and whose bilirubin is descending, a value of ≤ 3 X N is acceptable
-
Study treatment planned to start within 14 days of registration
-
Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
-
Signed, written informed consent
- Tumour size greater than 70mm
- Prior abdominal radiotherapy
- 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, or any Stage 1 endometrial carcinoma. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary 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 registration. 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Gemcitabine + Nab-paclitaxel * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm B Gemcitabine + Nab-paclitaxel * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm A Gemcitabine + Capecitabine * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm B Gemcitabine + Capecitabine * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm A mFOLFIRINOX * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm A Pancreatoduodenectomy (Whipple procedure) * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm B mFOLFIRINOX * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm B Stereotactic Radiotherapy (SBRT) * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine Arm B Pancreatoduodenectomy (Whipple procedure) * Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine
- Primary Outcome Measures
Name Time Method Locoregional control (Locoregional Response Rate LRR) Within 12 months of randomisation; To determine if the addition of SBRT to chemotherapy improves locoregional control;
- Secondary Outcome Measures
Name Time Method R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA) At surgery Compare R0 resection rates (\>1 mm)
Deterioration-Free Survival (DFS) (EORTC QLQ C30) The time until the first of the following events: a 10-point deterioration in health status from baseline, disease progression, death, or treatment discontinuation;up to 4 years To assess overall net clinical benefit of treatment
Overall Survival (OS) From the date of randomisation to date of death from any cause, or the date of last known alive; up to 4 years OS is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known alive. Participants will be censored at the date of commencement of the subsequent anti-cancer therapy.
Progression Free Survival (PFS) (RECIST v1.1) From randomisation to the time of first documented clinical or imaging relapse or date of death from any cause, whichever occurs first; up to 4 years Compare 12-month progression free survival
Safety (NCI CTCAE v5.0) Safety Assessment before each cycle of chemotherapy, post chemotherapy treatment, following SBRT and surgery (if applicable) then at 3, 6, 9 and 12 months post-randomisation and 6 monthly during year 2, 3 and 4 Compare acute and late side effects from chemotherapy +/- SBRT
Quality of Life (EORTC QLQ C30 and PAN26 QOL) Baseline, Day 1 of each cycle of chemotherapy, prior to SBRT, post initial chemotherapy +/- SBRT, prior to surgery, 30 days post end of treatment, at months 3, 6,9 and 12 post randomisation 6 monthly in years 2, 3 and 4. To assess the impact of the regimens on quality of life of patients
Surgical morbidity/mortality (Clavien grading system) At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years Length of stay, death within 30 days, frequency and severity of adverse events. Hospital admission during surgery will be calculated from day of surgery to date of discharge from acute care hospitalisation. The length of stay in acute hospital care will include intensive care admissions.
Pathological response rates (College of American Pathology Tumour Regression Grade TRG) At SRBT/surgery compared to baseline; Compare pathologic response rates of chemotherapy +/- SBRT
Radiological response rates (RECIST v1.1) at baseline. In SBRT arm, post-initial chemotherapy (prior to SBRT). In both arms, 4-6 weeks post completion of initial treatment (prior to surgery), 3 ,6, 9 and 12 monthly during year 2, 3 and 4. Compare radiologic response rates for chemotherapy +/- SBRT
Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology) At surgery Compare rates of surgical resection
Trial Locations
- Locations (11)
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
ICON Cancer Centre, Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia