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

Primary Purpose

Pancreatic Cancer

Status
Unknown status
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Stereotactic Radiotherapy (SBRT)
mFOLFIRINOX
Gemcitabine + Nab-paclitaxel
Gemcitabine + Capecitabine
Pancreatoduodenectomy (Whipple procedure)
Sponsored by
Australasian Gastro-Intestinal Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring stereotactic body radiotherapy, SBRT, chemotherapy, radiotherapy, surgery

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Chris O'Brien LifehouseRecruiting
  • St George HospitalRecruiting
  • Prince of Wales HospitalRecruiting
  • Royal North Shore HospitalRecruiting
  • Calvary Mater NewcastleRecruiting
  • Westmead HospitalRecruiting
  • ICON Cancer Centre, Gold Coast University HospitalRecruiting
  • Princess Alexandra HospitalRecruiting
  • Royal Adelaide HospitalRecruiting
  • Peter MacCallum Cancer CentreRecruiting
  • The Alfred HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm Description

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

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

Outcomes

Primary Outcome Measures

Locoregional control (Locoregional Response Rate LRR)
To determine if the addition of SBRT to chemotherapy improves locoregional control;

Secondary Outcome Measures

Safety (NCI CTCAE v5.0)
Compare acute and late side effects from chemotherapy +/- SBRT
Surgical morbidity/mortality (Clavien grading system)
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)
Compare radiologic response rates for chemotherapy +/- SBRT
Progression Free Survival (PFS) (RECIST v1.1)
Compare 12-month progression free survival
Pathological response rates (College of American Pathology Tumour Regression Grade TRG)
Compare pathologic response rates of chemotherapy +/- SBRT
Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology)
Compare rates of surgical resection
R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA)
Compare R0 resection rates (>1 mm)
Quality of Life (EORTC QLQ C30 and PAN26 QOL)
To assess the impact of the regimens on quality of life of patients
Deterioration-Free Survival (DFS) (EORTC QLQ C30)
To assess overall net clinical benefit of treatment
Overall Survival (OS)
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.

Full Information

First Posted
February 4, 2019
Last Updated
October 15, 2021
Sponsor
Australasian Gastro-Intestinal Trials Group
Collaborators
Trans Tasman Radiation Oncology Group, Australian Government Department of Health and Ageing
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1. Study Identification

Unique Protocol Identification Number
NCT04089150
Brief Title
MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Acronym
MASTERPLAN
Official Title
MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
August 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Australasian Gastro-Intestinal Trials Group
Collaborators
Trans Tasman Radiation Oncology Group, Australian Government Department of Health and Ageing

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
stereotactic body radiotherapy, SBRT, chemotherapy, radiotherapy, surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
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 Title
Arm B
Arm Type
Experimental
Arm Description
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 Type
Radiation
Intervention Name(s)
Stereotactic Radiotherapy (SBRT)
Other Intervention Name(s)
SBRT, Stereotactic Body Radiotherapy
Intervention Description
40 Gray (Gy) in 5 fractions, 2-3 fractions per week over two weeks, 8 Gy per fraction
Intervention Type
Drug
Intervention Name(s)
mFOLFIRINOX
Other Intervention Name(s)
modified regimen of oxaliplatin, leucovorin, irinotecan, and fluorouracil (5-FU)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Gemcitabine + Nab-paclitaxel
Other Intervention Name(s)
Gemcitabine + Abraxane
Intervention Description
Day 1, Day 8 and Day 15 gemcitabine 1000mg/m2 + nab-paclitaxel 125mg/m2 28-day cycle, 3 cycles
Intervention Type
Drug
Intervention Name(s)
Gemcitabine + Capecitabine
Other Intervention Name(s)
GemCap
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Pancreatoduodenectomy (Whipple procedure)
Other Intervention Name(s)
Whipple
Intervention Description
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.
Primary Outcome Measure Information:
Title
Locoregional control (Locoregional Response Rate LRR)
Description
To determine if the addition of SBRT to chemotherapy improves locoregional control;
Time Frame
Within 12 months of randomisation;
Secondary Outcome Measure Information:
Title
Safety (NCI CTCAE v5.0)
Description
Compare acute and late side effects from chemotherapy +/- SBRT
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
Title
Surgical morbidity/mortality (Clavien grading system)
Description
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.
Time Frame
At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years
Title
Radiological response rates (RECIST v1.1)
Description
Compare radiologic response rates for chemotherapy +/- SBRT
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.
Title
Progression Free Survival (PFS) (RECIST v1.1)
Description
Compare 12-month progression free survival
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
Title
Pathological response rates (College of American Pathology Tumour Regression Grade TRG)
Description
Compare pathologic response rates of chemotherapy +/- SBRT
Time Frame
At SRBT/surgery compared to baseline;
Title
Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology)
Description
Compare rates of surgical resection
Time Frame
At surgery
Title
R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA)
Description
Compare R0 resection rates (>1 mm)
Time Frame
At surgery
Title
Quality of Life (EORTC QLQ C30 and PAN26 QOL)
Description
To assess the impact of the regimens on quality of life of patients
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.
Title
Deterioration-Free Survival (DFS) (EORTC QLQ C30)
Description
To assess overall net clinical benefit of treatment
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
Title
Overall Survival (OS)
Description
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.
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
Other Pre-specified Outcome Measures:
Title
Exploratory biomarker analysis of blood
Description
The list of blood biomarkers and their measurement will be updated when confirmed.
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
Title
Exploratory biomarker analysis of tissue
Description
The list of tissue biomarkers and their measurement will be updated when confirmed.
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.
Title
ePRO Acceptability
Description
Proportion of patients who are willing to use electronic device vs. paper format, Analysis of demographic data and assessing data quality between the group
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
NHMRC CTC
Phone
+61 (0) 2 9562 5000
Email
masterplan@ctc.usyd.edu.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Oar
Organizational Affiliation
ICON Gold Coast University Hospital, Southport, Queensland, AUS
Official's Role
Study Chair
Facility Information:
Facility Name
Chris O'Brien Lifehouse
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Individual Site Status
Recruiting
Facility Name
Calvary Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Individual Site Status
Recruiting
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Name
ICON Cancer Centre, Gold Coast University Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Recruiting
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.

Learn more about this trial

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

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