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MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease (MASTERPLAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04089150
Recruitment Status : Recruiting
First Posted : September 13, 2019
Last Update Posted : October 22, 2021
Sponsor:
Collaborators:
Trans Tasman Radiation Oncology Group
Australian Government Department of Health and Ageing
Information provided by (Responsible Party):
Australasian Gastro-Intestinal Trials Group

Tracking Information
First Submitted Date  ICMJE February 4, 2019
First Posted Date  ICMJE September 13, 2019
Last Update Posted Date October 22, 2021
Actual Study Start Date  ICMJE October 1, 2019
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
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;
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Safety (NCI CTCAE v5.0) [ Time Frame: 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
  • Surgical morbidity/mortality (Clavien grading system) [ Time Frame: 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.
  • Radiological response rates (RECIST v1.1) [ Time Frame: 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
  • Progression Free Survival (PFS) (RECIST v1.1) [ Time Frame: 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
  • Pathological response rates (College of American Pathology Tumour Regression Grade TRG) [ Time Frame: At SRBT/surgery compared to baseline; ]
    Compare pathologic response rates of chemotherapy +/- SBRT
  • Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology) [ Time Frame: At surgery ]
    Compare rates of surgical resection
  • R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA) [ Time Frame: At surgery ]
    Compare R0 resection rates (>1 mm)
  • Quality of Life (EORTC QLQ C30 and PAN26 QOL) [ Time Frame: 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
  • Deterioration-Free Survival (DFS) (EORTC QLQ C30) [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 11, 2019)
  • Exploratory biomarker analysis of blood [ Time Frame: baseline, prior to SBRT (Arm B only), insertion of fiducial markers (Arm B, optional), post initial treatment, at surgery (optional, at selected sites), 6 and12 months post randomisation and at progression, up to 5 years ]
    The list of blood biomarkers and their measurement will be updated when confirmed.
  • Exploratory biomarker analysis of tissue [ Time Frame: Diagnosis (archival tissue), at time of fiducial insertion (Arm B, optional), surgical resection (for resectable patients) and at time of progression (optional), up to 5 years. ]
    The list of tissue biomarkers and their measurement will be updated when confirmed.
  • ePRO Acceptability [ Time Frame: Baseline, Day 1 of each cycle of chemotherapy, 2 weeks post initial chemotherapy(SBRT arm), 4-6 weeks post initial chemotherapy +/- SBRT, 30 days post end of treatment, at months 3, 6,9 and 12 post randomisation 6 monthly in years 2, 3 and 4. ]
    Proportion of patients who are willing to use electronic device vs. paper format, Analysis of demographic data and assessing data quality between the group
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Official Title  ICMJE MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE
  • Radiation: Stereotactic Radiotherapy (SBRT)
    40 Gray (Gy) in 5 fractions, 2-3 fractions per week over two weeks, 8 Gy per fraction
    Other Names:
    • SBRT
    • Stereotactic Body Radiotherapy
  • Drug: mFOLFIRINOX
    • Day 1: oxaliplatin 85mg/m2 + irinotecan 150mg/m2 + leucovorin 50mg
    • 5-FU 2400mg/m2 continuous IV infusion, 46 hour continuous infusion
    • 14-day cycle, 6 cycles
    Other Name: modified regimen of oxaliplatin, leucovorin, irinotecan, and fluorouracil (5-FU)
  • Drug: Gemcitabine + Nab-paclitaxel
    • Day 1, Day 8 and Day 15 gemcitabine 1000mg/m2 + nab-paclitaxel 125mg/m2
    • 28-day cycle, 3 cycles
    Other Name: Gemcitabine + Abraxane
  • Drug: Gemcitabine + Capecitabine
    • Week 1, 2 and 3, qw: 1000 mg/m2 gemcitabine
    • 21 days continuous: 830 mg/m2 oral capecitabine + 7 days rest
    • 28-day cycle, 3 cycles
    Other Name: GemCap
  • Procedure: Pancreatoduodenectomy (Whipple procedure)
    R0 resection. When the tumour is within the head of the pancreas, a standard Whipple's procedure and level 2/3 dissection with modification to obtain margin clearance will be offered. For lesions in the tail, a standard modular resection will be offered.
    Other Name: Whipple
Study Arms  ICMJE
  • Active Comparator: Arm A
    • 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
    Interventions:
    • Drug: mFOLFIRINOX
    • Drug: Gemcitabine + Nab-paclitaxel
    • Drug: Gemcitabine + Capecitabine
    • Procedure: Pancreatoduodenectomy (Whipple procedure)
  • Experimental: Arm B
    • 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
    Interventions:
    • Radiation: Stereotactic Radiotherapy (SBRT)
    • Drug: mFOLFIRINOX
    • Drug: Gemcitabine + Nab-paclitaxel
    • Drug: Gemcitabine + Capecitabine
    • Procedure: Pancreatoduodenectomy (Whipple procedure)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2019)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 30, 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma
  • Any of the following

    1. T3 (tumour >4 cm)
    2. Extrapancreatic extension
    3. Node positive (stage IIB)
    4. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: NHMRC CTC +61 (0) 2 9562 5000 masterplan@ctc.usyd.edu.au
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04089150
Other Study ID Numbers  ICMJE CTC 0245/AGITG AG0118PS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description:

The study will be conducted in accordance with applicable Privacy Acts and Regulations. All data generated in this study will remain confidential. All information will be stored securely at the NHMRC CTC, University of Sydney and will only be available to people directly involved with the study.

Personal data identifying trial participants will be held securely at the NHMRC CTC for the purpose of follow up if the patient is unable to/wishes to discontinue clinic based follow-up.

Current Responsible Party Australasian Gastro-Intestinal Trials Group
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Australasian Gastro-Intestinal Trials Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Trans Tasman Radiation Oncology Group
  • Australian Government Department of Health and Ageing
Investigators  ICMJE
Study Chair: Andrew Oar ICON Gold Coast University Hospital, Southport, Queensland, AUS
PRS Account Australasian Gastro-Intestinal Trials Group
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP