NCT04089150UnknownPhase 2
MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Australasian Gastro-Intestinal Trials Group11 sites in 1 country120 target enrollmentStarted: October 1, 2019Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Enrollment
- 120
- Locations
- 11
- Primary Endpoint
- Locoregional control (Locoregional Response Rate LRR)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Arm A
Active Comparator
- 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
Intervention: mFOLFIRINOX (Drug)
Arm A
Active Comparator
- 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
Intervention: Gemcitabine + Nab-paclitaxel (Drug)
Arm A
Active Comparator
- 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
Intervention: Gemcitabine + Capecitabine (Drug)
Arm A
Active Comparator
- 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
Intervention: Pancreatoduodenectomy (Whipple procedure) (Procedure)
Arm B
Experimental
- 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
Intervention: Stereotactic Radiotherapy (SBRT) (Radiation)
Arm B
Experimental
- 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
Intervention: mFOLFIRINOX (Drug)
Arm B
Experimental
- 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
Intervention: Gemcitabine + Nab-paclitaxel (Drug)
Arm B
Experimental
- 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
Intervention: Gemcitabine + Capecitabine (Drug)
Arm B
Experimental
- 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
Intervention: Pancreatoduodenectomy (Whipple procedure) (Procedure)
Outcomes
Primary Outcomes
Locoregional control (Locoregional Response Rate LRR)
Time Frame: Within 12 months of randomisation;
To determine if the addition of SBRT to chemotherapy improves locoregional control;
Secondary Outcomes
- R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA)(At surgery)
- 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)
- 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)
- 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)
- 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)
- 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.)
- Surgical morbidity/mortality (Clavien grading system)(At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years)
- Pathological response rates (College of American Pathology Tumour Regression Grade TRG)(At SRBT/surgery compared to baseline;)
- 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.)
- Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology)(At surgery)
Investigators
Study Sites (11)
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