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

Sponsor
Australasian Gastro-Intestinal Trials Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04089150
Collaborator
Trans Tasman Radiation Oncology Group (Other), Australian Government Department of Health and Ageing (Other)
120
11
2
46.9
10.9
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Radiation: Stereotactic Radiotherapy (SBRT)
  • Drug: mFOLFIRINOX
  • Drug: Gemcitabine + Nab-paclitaxel
  • Drug: Gemcitabine + Capecitabine
  • Procedure: Pancreatoduodenectomy (Whipple procedure)
Phase 2

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
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Actual Study Start Date :
Oct 1, 2019
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
Aug 30, 2023

Arms and Interventions

Arm Intervention/Treatment
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

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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Whipple
  • 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

    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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Whipple
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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.

    3. 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

    4. 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

    5. Pathological response rates (College of American Pathology Tumour Regression Grade TRG) [At SRBT/surgery compared to baseline;]

      Compare pathologic response rates of chemotherapy +/- SBRT

    6. Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology) [At surgery]

      Compare rates of surgical resection

    7. 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)

    8. 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

    9. 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

    10. 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.

    Other Outcome Measures

    1. Exploratory biomarker analysis of blood [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.

    2. Exploratory biomarker analysis of tissue [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.

    3. ePRO Acceptability [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    2 St George Hospital Kogarah New South Wales Australia 2217
    3 Prince of Wales Hospital Randwick New South Wales Australia 2031
    4 Royal North Shore Hospital St Leonards New South Wales Australia 2065
    5 Calvary Mater Newcastle Waratah New South Wales Australia 2298
    6 Westmead Hospital Westmead New South Wales Australia 2145
    7 ICON Cancer Centre, Gold Coast University Hospital Southport Queensland Australia 4215
    8 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    9 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    10 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    11 The Alfred Hospital Melbourne Victoria Australia 3004

    Sponsors and Collaborators

    • Australasian Gastro-Intestinal Trials Group
    • Trans Tasman Radiation Oncology Group
    • Australian Government Department of Health and Ageing

    Investigators

    • Study Chair: Andrew Oar, ICON Gold Coast University Hospital, Southport, Queensland, AUS

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Australasian Gastro-Intestinal Trials Group
    ClinicalTrials.gov Identifier:
    NCT04089150
    Other Study ID Numbers:
    • CTC 0245/AGITG AG0118PS
    First Posted:
    Sep 13, 2019
    Last Update Posted:
    Oct 22, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by Australasian Gastro-Intestinal Trials Group
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 22, 2021