Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000335291
Ethics application status
Approved
Date submitted
23/02/2018
Date registered
6/03/2018
Date last updated
16/06/2023
Date data sharing statement initially provided
9/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer: A Multicentre Randomised Study (DYNAMIC- Pancreas)
Scientific title
Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer: A Multicentre Randomised Study (DYNAMIC- Pancreas)
Secondary ID [1] 294109 0
ctDNA-09
Universal Trial Number (UTN)
U1111-1209-6200
Trial acronym
DYNAMIC-Pancreas
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 306702 0
Condition category
Condition code
Cancer 305803 305803 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a prospective, multi-centre, randomised study enrolling 438 patients with localised pancreatic cancer who are undergoing either neoadjuvant (peri-operative) therapy followed by “curative” surgery (R0 or R1 resection) (n=350) or immediate “curative” surgery who would routinely be offered adjuvant chemotherapy (n=88).

Patients who have received radiotherapy prior to surgery will be eligible for the study.

This study will randomise patients who have received neoadjuvant chemotherapy 1:1 into either a non-biomarker-driven, standard of care adjuvant treatment arm (Cohort A) or a ctDNA-informed biomarker-driven adjuvant treatment arm (Cohort B). The adjuvant chemotherapy treatment of Cohort B participants will be guided by the post-operative ctDNA result of individual participants. Randomisation will occur after the post-operative week 4-6 blood collection and receipt of sufficient tumour tissue for ctDNA analysis.

Patients who did not receive neoadjuvant chemotherapy and instead underwent immediate “curative” surgery will be enrolled into a separate non-randomised biomarker-driven adjuvant treatment group (Cohort C), where the adjuvant chemotherapy treatment will be guided by the post-operative ctDNA results of individual participants.

Patients should be screened and consented within 6 weeks after surgery, and tumour samples made available within 5 working days of consent and within 7 weeks post-surgery for mutation analysis. All participants will have the first blood specimen for ctDNA analysis collected 4-6 weeks post-surgery (ctDNA-1A). Clinicians are to nominate their standard of care adjuvant chemotherapy regimen at the time of enrolment and (if applicable) prior to randomisation. Adjuvant chemotherapy must be scheduled to start within 12 weeks of surgery.

Participants and clinicians in Cohort A will be blinded to their ctDNA-1A results and participants will receive adjuvant chemotherapy as per standard of care. Clinicians may commence chemotherapy treatment of participants in Cohort A with a standard of care regimen no sooner than 6 weeks post-operatively.

For ctDNA-informed participants (Cohorts B and C), the ctDNA-1A results will be made available to the treating clinician approximately 4-5 weeks after receipt of sufficient tumour tissue for mutation analysis. Adjuvant chemotherapy will commence after the ctDNA-1A result becomes available and will be switched or "escalated”, or “de-escalated” according to the participants’ ctDNA-1A result. If the treating clinician wishes to commence chemotherapy before the ctDNA-1A result is available, patients may commence on standard of care chemotherapy no sooner than 6 weeks post-operatively (the exact timing will depend on the number of weeks post-surgery the patient was consented and the adjuvant chemotherapy regimen), and then switch to a strategy informed by the ctDNA result once this has become available (if the patient management needs to be changed to comply with the protocol). Patients who are “ctDNA-negative” will be managed with a “de-escalated” adjuvant treatment strategy if the treating clinician considers this appropriate. Patients who are “ctDNA-positive” will be managed with an “escalated” or “switched” adjuvant treatment strategy if fit to receive more intensive therapy (see treatment regimens below).

The total number of additional study blood collections scheduled for ctDNA analysis will depend on the duration of adjuvant chemotherapy:
All participants will have ctDNA-1B bloods collected immediately prior to the commencement of adjuvant chemotherapy and once chemotherapy is completed (ctDNA-3). Participants receiving 5-6 months of adjuvant chemotherapy will have a ctDNA blood collection scheduled approximately mid-chemotherapy (ctDNA-2A). Patients receiving 3-4 months of adjuvant chemotherapy will not be required to provide a mid-chemotherapy ctDNA blood sample.
If a participant is found to have progressive disease prior to the completion of planned adjuvant treatment, a final blood collection (ctDNA-2B) should be performed at the time of disease progression and prior to commencing any further systemic therapy (in these participants, the end-of-treatment ctDNA-3 collection will no longer be required).
Results for ctDNA-1B, -2A, -2B and -3 blood collections will not be routinely made available to the patients or treating clinicians (results may be made available on a case-by-case basis at clinician and/or patient request).
Formalin-fixed paraffin-embedded tumour tissue samples and the study blood samples will be shipped to the Vogelstein laboratory at Johns Hopkins USA for ctDNA analysis.

Treatment regimens:

Chemotherapy dose should be calculated at actual body weight. Body surface area dosing will be managed as per institutional standard of care with regards to dose capping. Dosage modifications and reductions to adjuvant chemotherapy in line with standard clinical care are acceptable at the clinicians’ discretion.

Suggested combination chemotherapy regimens include 24 weeks of the following treatment options:

1. Gemcitabine plus Capecitabine, Cycle frequency: 28 days
a. Gemcitabine 1000 mg/m2 Intravenously Day 1, 8, 15
b. Capecitabine 830 mg/m2 Orally Twice daily, Day 1-21, 7 day rest

2. Modified FOLFIRINOX, Cycle frequency: 14 days
a. Oxaliplatin 85mg/2 Intravenously Day 1
b. Irinotecan 150mg/m2 Intravenously Day 1
c. Leucovorin 50mg Intravenously Day 1
d. Fluorouracil 2400mg/m2 Continuous Intravenous Infusion pump over 46 hours Day 1
(The use of G-CSF (granulocyte colony stimulating factor) is permitted. Its use should be in accordance with institutional guidelines)

3. Gemcitabine plus nab-paclitaxel (Abraxane), Cycle frequency: 28 days
a. Nab-paclitaxel 125mg/m2 Intravenously Day 1,8,15
b. Gemcitabine 1000mg/m2 Intravenously Day 1,8,15

Study Treatments

Cohort A – Neoadjuvant, non-biomarker driven dealer's choice standard of care adjuvant chemotherapy arm. All participants randomised to Cohort A must have received neoadjuvant (peri-operative) chemotherapy prior to surgery. Standard of care chemotherapy should be administered with the intent of completing a total of 6 months of peri-operative chemotherapy with modified FOLFIRINOX as the recommended treatment.

Cohort B – Neoadjuvant biomarker-driven arm. All participants randomised to Cohort B must have received neoadjuvant (peri-operative) chemotherapy prior to surgery. Adjuvant chemotherapy will be offered according to the ctDNA result.

ctDNA negative participants may have their chemotherapy “de-escalated” and receive a SHORTER duration (recommended 3 months) of adjuvant modified FOLFIRINOX. The duration of the adjuvant treatment may be reduced at the clinician’s discretion if a longer course of neoadjuvant chemotherapy was administered. The recommendation is for a total of 6 months of peri-operative chemotherapy with at least 2 months in the post-operative setting.

ctDNA positive participants may have their chemotherapy “switched” and receive a recommended 4-6 months of adjuvant gemcitabine doublet therapy (clinicians choice of nab-paclitaxel [Abraxane] or capecitabine). The duration of treatment will be at the clinician’s discretion; the length of the pre-operative treatment may be a factor in determining the duration of adjuvant chemotherapy.

Cohort C - Immediate resection, biomarker-driven arm. Clinicians must indicate the intended standard of care adjuvant treatment (either modified FOLFIRINOX or gemcitabine-based doublet therapy, e.g. gemcitabine plus capecitabine) at the time of patient enrolment.
ctDNA negative participants may have their chemotherapy “de-escalated” to receive a SHORTER duration (recommended 3-4 months) of whatever was the clinician’s choice standard of care adjuvant therapy.
ctDNA positive participants may have their chemotherapy “escalated” to receive a LONGER duration (recommended 6 months) of whatever was the clinician’s choice of standard of care adjuvant therapy was (modified FOLFIRINOX or gemcitabine plus capecitabine). ctDNA positive participants, for whom the adjuvant therapy intent was gemcitabine doublet, also have the option of having their treatment “switched” to receive up to 6 months of adjuvant gemcitabine plus nab-paclitaxel (Abraxane) therapy at the clinician's discretion.

It is anticipated that 438 eligible patients will be enrolled over a 54-month accrual period. Details of adjuvant chemotherapy administered including start and stop dates, dose received, dose reduction, reason for dose reduction/interruption and reason for stopping treatment will be recorded. Serious Unexpected Serious Adverse Reactions (SUSAR) for patients treated with either modified FOLFIRINOX or combination Gemcitabine plus Abraxane, and treatment-related hospitalisation for all patients will also be collected.

All patients will be followed until death or study completion. Patients will be followed up as per standard of care, every 3 months for 24 months, then 6-monthly for the next 3 years. The trial will be considered complete after the last patient enrolled has had 2 years of follow-up. It is anticipated that this study will run for approximately 6.5 years.

Interim Analysis: A review of the ctDNA results turn-around time will be conducted after the first 50 participants have been recruited. The study will be routinely monitored by the AGITG’s Independent Data Safety and Monitoring Committee (IDSMC) although no formal interim analyses are yet planned.
Intervention code [1] 300394 0
Early detection / Screening
Intervention code [2] 300395 0
Treatment: Drugs
Comparator / control treatment
Standard of Care Arm (Cohort A)

All patients randomised to the Cohort A: Standard of Care Arm must have received neoadjuvant (peri-operative) chemotherapy prior to surgery. Cohort A participants will receive adjuvant chemotherapy as per standard of care at their clinician's discretion.. It is recommended that treatment be administered with the intent of completing a total of 6 months of peri-operative chemotherapy with modified FOLFIRINOX (fluorouracil [5-FU], Leucovorin, Irinotecan, Oxaliplatin).

Participants in Cohort A and clinicians will be blinded to their ctDNA results.
Control group
Active

Outcomes
Primary outcome [1] 304874 0
Patient 2-year recurrence-free survival: a comparison of ctDNA-driven treatment outcomes (Cohorts B and C) against standard of care management treatment outcomes in the control arm (Cohort A).
For ctDNA analysis, archived patient formalin-fixed paraffin-embedded tumour tissue samples collected post-enrolment will be used for mutation analysis of hotspot mutations in genes frequently altered in pancreatic cancer. The mutation identified in each patient's tumour tissue will be queried and quantified in the plasma samples (i.e. circulating tumour DNA) obtained from on study blood collections. Mutation analysis will be performed by the laboratories at Johns Hopkins USA using the Safe-SeqS assay.
Timepoint [1] 304874 0
Blood collections for plasma ctDNA analysis are scheduled to occur at week 4-6 post surgery (ctDNA-1A), immediately prior to the commencement of adjuvant chemotherapy (ctDNA-1B), at approximately 3 months (mid-way) of chemotherapy (ctDNA-2A) (only collected for adjuvant chemotherapy regimens of 5-6 months duration), and after chemotherapy has been completed (ctDNA-3). An additional blood sample may be collected if patients are found to have documented progressive disease while undergoing adjuvant therapy (ctDNA-2B), and for these progressive disease participants, the ctDNA-3 sample will no longer be required.

ctDNA positivity at the different stages detailed above will be compared with serum-CA 19-9 counterparts at the same stage.

The primary outcome timepoint analysis will be the comparison of the standard of care Cohort A with the ctDNA biomarker-informed “escalated”/”switched” Cohorts B and C with respect to recurrence-free survival. This analysis will be conducted when all recruited patients have completed their adjuvant therapy and the last participant enrolled has had 24 months of follow-up after pancreatic resection or the percentage available 2-year information is sufficient to warrant the final analysis to be conducted. Based on an estimated accrual period of approximately 54 months, analysis of the primary timepoint would occur at approximately 78 months from the commencement of the study.
Secondary outcome [1] 343443 0
Correlation of post-operative and end-of-treatment ctDNA results with recurrence -free and overall survival. Comparisons will be made (1) between treatment arms as per intention-to-treat, (2) between participants with and without detectable ctDNA at baseline, (3) with and without detectable ctDNA post-surgery and (4) with and without detectable ctDNA at end of therapy. Survival analysis will be carried out when all participants have a minimum 2-year follow-up after pancreatic resection or the percentage available 2-year information is sufficient to warrant the final analysis to be conducted.
Outcomes will be assessed by clinical review, blood tumour marker CA 19-9 testing and tumour imaging with CT scans of chest/abdomen/pelvis (as per standard of care).
Timepoint [1] 343443 0
Schedule of Assessments: patients will be followed up for recurrence and survival data collection at clinical visits every 3 months from randomisation for 24 months, then 6-monthly for the next 3 years with CA 19-9 testing and CT scans conducted as per standard of care.

Eligibility
Key inclusion criteria
1. Subjects who have undergone complete macroscopic resection for adenocarcinoma of the pancreas (R0 or R1 resection) with “curative” intent.
2. A representative tumour sample is available for molecular testing within 6 weeks after surgery.
3. Subjects is fit for adjuvant chemotherapy.
4. Subject has ECOG performance status 0-2.
5. Subject is to attend for administration of adjuvant therapy.
6. Subject is accessible for follow up.
7. No evidence of malignant ascites, liver metastasis, spread to other distant abdominal organs, peritoneal metastasis, spread to extra-abdominal organs - Subject to have had a CT chest/ abdomen/ pelvis scan within 12 weeks prior to randomisation.
8. Fully informed written consent given
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of another primary cancer within the last 3 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix.
2. Patient has inadequate organ function:
a. Moderate/severe renal impairment (GFR<30 ml/min), as calculated by the Cockcroft and Gault equation
b. Absolute neutrophil count <1.0x109/L
c. Platelet count <75x109/L
d. Haemoglobin <80 g/L
e. Aspartate aminotransferase/Alanine aminotransferase >2.5 x upper limit of normal
3. Patient has a medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol.
4. Patient has TNM stage IV disease.
5. Patient has R2 resection status.
6. Patient has clinically significant cardiovascular disease - i.e. active or <12 months since e.g. cerebrovascular accident, myocardial infarction, unstable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation to Arm A (Standard of Care) or Arm B (ctDNA-informed) is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be randomised using a permuted block design with random block size. The blocking factor will be the centre. Randomisation lists will be generated using a computer-based randomisation algorithm module.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Statistical methods / analysis
It is anticipated that 438 eligible patients will be enrolled over a 54-month accrual period. All patients will be followed until death or study completion. The trial will be considered complete after the last patient enrolled has had 2 years of follow-up. It is anticipated that this study will run for approximately 6.5 years.

There are no published data regarding ctDNA positivity rates in early stage resected pancreatic cancer patients although it is anticipated that ~40% of patients will be ctDNA positive. The recently reported PRODIGE 24 study quotes a 50% recurrence rate at 2 years with mFOLFIRINOX versus 69% recurrence with gemcitabine alone.

For participants in the ctDNA positive group who have received neoadjuvant therapy, it is anticipated that 140 participants would fall in to this cohort, of which 70 will receive biomarker guided therapy. The median survival of this population is expected to be approximately 20.8 months. Assuming a duration of accrual of 36 months and participants followed up for at least 24 months, for this sample size randomised in a 1:1 allocation, if there was no advantage with the “escalating” treatment, we would expect 39 recurrences in each group. As this cohort is a randomised phase II design, to ascertain activity a 90% confidence is employed as opposed to the usual 95%. This design will thus estimate the hazard ratio (HR) Gemcitabine/nab paclitaxel (Abraxane): mFOLFIRINOX for recurrence free with a 90% confidence interval bounded by [HR/1.451 to HR*1.451]. If the upper limit of this CI is less than 1 (corresponding to HR<0.689), then we would conclude GEM/Abraxane to be superior to mFOLFIRINOX and worthy of further investigation.

It is recognised that this trial is underpowered to detect such an effect. Consequently, if the observed HR is larger than 0.689, Gemcitabine/nab paclitaxel (Abraxane) may still have sufficient clinical activity to warrant further investigation but a decision to investigate further would be based on additional information related to the observed HR such as QoL and other outcomes. Whilst this is a phase II design, if prior to the end of the study, the number of events is sufficiently large, the design may be re-assessed and converted to a larger phase III trial.

210 of the 350 participants are expected to be ctDNA negative and it is anticipated that the 2-year recurrence-free survival rate will be ~65%. Characteristics of this cohort will be presented as a descriptive analysis.

For sites who standard of care is immediate resection, participants can be enrolled into a non-randomised single-arm biomarker guided study (Cohort C) in order to gain further insight into the use of such a strategy. 88 participants would be expected to fall into this category and all would receive ctDNA managed therapy. Of these 88, 35 would be ctDNA positive and 53 ctDNA negative. For this separate Cohort C, analysis for: (i) the ctDNA positive group - a total of 35 participants (based on Fleming’s single-arm design, 80% power, 95% confidence) would be required to rule out a 2-year 45% recurrence rate in favour of a more interesting rate of 66%.; (ii) the ctDNA negative group will be described with respect to the 2-year recurrence rate as well as other clinical and patient outcomes.

The primary analysis for the ctDNA positive cohort will be the comparison of the HR of the two cohorts (SOC vs escalation) with respect to recurrence-free survival and the 90% CI for this effect as described above (Cohorts A & B). For this cohort, the recurrence-free survival as measured from the date randomisation to the time of recurrence or last known alive will be compared using the proportional hazards regression. Overall survival as measured from the date of randomisation to the time of death from any cause or last known alive and other time-to-event outcomes will be compared using statistical methods (proportional hazards regression, logrank and landmark analyses) as appropriate. Exploratory modelling will be performed using multivariable regression techniques (linear, logistic proportional hazards etc.) to investigate and adjust any treatment effect by stratification factors and prognostic factors. The primary analysis will be consistent with the intention to treat principle.

Based on these assumptions, this study has been designed with a focus on the neo-adjuvant (peri-operative) cohort of ctDNA positive participants (n=140). For sites whose standard of care is immediate resection, participants can be enrolled into a separate non-randomised single-arm biomarker guided cohort (n=88) in order to gain further insight into the use of such a strategy.

Several secondary outcomes analyses will be undertaken including ctDNA turn-around time, proportion of participants completing planned study treatment, health economic impact, recurrence-free survival and overall survival.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
26/03/2018
Actual
20/03/2019
Date of last participant enrolment
Anticipated
Actual
9/11/2022
Date of last data collection
Anticipated
9/11/2024
Actual
Sample size
Target
438
Accrual to date
Final
118
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 10093 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 10096 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 10097 0
The Northern Hospital - Epping
Recruitment hospital [4] 10099 0
Western Hospital - Footscray - Footscray
Recruitment hospital [5] 10101 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 10102 0
Melbourne Private Hospital - Parkville
Recruitment hospital [7] 14159 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [8] 14160 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [9] 14161 0
Frankston Hospital - Frankston
Recruitment hospital [10] 14162 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [11] 14163 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [12] 14164 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [13] 17506 0
Royal Hobart Hospital - Hobart
Recruitment hospital [14] 17507 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [15] 17508 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [16] 17509 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [17] 17510 0
Epworth Eastern Hospital - Box Hill
Recruitment hospital [18] 17511 0
Epworth Richmond - Richmond
Recruitment hospital [19] 17512 0
Epworth Freemasons (Clarendon Street) - East Melbourne
Recruitment hospital [20] 17513 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [21] 17514 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [22] 17515 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [23] 17516 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 31244 0
2200 - Bankstown
Recruitment postcode(s) [2] 27132 0
2290 - Gateshead
Recruitment postcode(s) [3] 27134 0
2298 - Waratah
Recruitment postcode(s) [4] 27133 0
2305 - New Lambton Heights
Recruitment postcode(s) [5] 31243 0
2485 - Tweed Heads
Recruitment postcode(s) [6] 31238 0
2500 - Wollongong
Recruitment postcode(s) [7] 21633 0
3000 - Melbourne
Recruitment postcode(s) [8] 31242 0
3002 - East Melbourne
Recruitment postcode(s) [9] 21630 0
3050 - Parkville
Recruitment postcode(s) [10] 21636 0
3052 - Parkville
Recruitment postcode(s) [11] 27129 0
3065 - Fitzroy
Recruitment postcode(s) [12] 21634 0
3076 - Epping
Recruitment postcode(s) [13] 31241 0
3121 - Richmond
Recruitment postcode(s) [14] 21637 0
3128 - Box Hill
Recruitment postcode(s) [15] 31240 0
3128 - Box Hill
Recruitment postcode(s) [16] 27130 0
3144 - Malvern
Recruitment postcode(s) [17] 27131 0
3199 - Frankston
Recruitment postcode(s) [18] 31246 0
4029 - Herston
Recruitment postcode(s) [19] 31245 0
4575 - Birtinya
Recruitment postcode(s) [20] 31239 0
5042 - Bedford Park
Recruitment postcode(s) [21] 31237 0
6150 - Murdoch
Recruitment postcode(s) [22] 31236 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 298745 0
Charities/Societies/Foundations
Name [1] 298745 0
Marcus Foundation
Country [1] 298745 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group
Address
GI Cancer Institute @Lifehouse
Level 6, 119-143 Missenden Rd
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 297918 0
Other
Name [1] 297918 0
The Walter and Eliza Hall Institute of Medical Research
Address [1] 297918 0
1G Royal Parade
Parkville
VIC 3052
Country [1] 297918 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299684 0
Melbourne Health
Ethics committee address [1] 299684 0
Level 2
South West
300 Grattan Street
Parkville Victoria 3050
Ethics committee country [1] 299684 0
Australia
Date submitted for ethics approval [1] 299684 0
26/04/2017
Approval date [1] 299684 0
03/07/2017
Ethics approval number [1] 299684 0
HREC/17/MH/38

Summary
Brief summary
Pancreatic cancer cells have DNA mutations that are not present in normal cells. For some people, cancer-specific DNA can be found circulating in their bloodstream after they had surgery to remove their pancreatic cancer. This tumour-specific DNA may be evidence that some cancer cells have escaped before the pancreatic cancer was removed. The DYNAMIC-Pancreas study aims to see whether a test called “circulating tumour DNA” can be used to decide the type and duration of post-surgery chemotherapy.

Who is it for?
You may be eligible to join this study if you are aged 18 years or more and have undergone curative surgery for localised pancreatic cancer and have been recommended adjuvant chemotherapy. You will still be eligible if you had neoadjuvant treatment prior to surgery.

Study Details.
All participants in this study will have blood drawn for circulating tumour DNA analysis during week 4-6 post-surgery, and throughout chemotherapy treatment (up to 3 times).
Participants that had neoadjuvant therapy prior to surgery, will be randomly allocated to one of two treatment groups, where the choice of chemotherapy regimen will be made prior to randomisation: One group will receive the standard of care treatment of modified FOLFIRINOX – a combination of fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin. The other group will have their treatment based on their circulating tumour DNA blood test results. Patients with a positive test will be offered an alternative chemotherapy than the standard treatment. Patients with a negative test will be offered a shorter duration of the standard treatment.
Participants that did not have neoadjuvant therapy prior to surgery, will be placed in a separate, non-randomised group. All participants in this group will have their treatment selection based on their circulating tumour DNA blood test results. Patients with a positive test will be offered an alternative chemotherapy than the standard treatment or a longer duration of the standard treatment. Patients with a negative test will be offered a shorter duration of the standard treatment.
All patients will be followed up every 3 months for 2 years, then every 6 months up to year 5. Follow up includes blood tests and radiological assessments. It is hoped that this study will provide evidence that using a test to look for the presence or absence of circulating tumour DNA can help guide the type or duration of adjuvant chemotherapy used after pancreatic cancer surgery.. This test may reduce the number of patients that have detectable circulating tumour DNA after completing adjuvant chemotherapy, compared to standard of care treatment. This may in turn demonstrate that management of pancreatic cancer based on circulating tumour DNA results is superior to the current standard of care treatment.
Trial website
none
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 81286 0
Dr Belinda Lee
Address 81286 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville
VIC 3052
Country 81286 0
Australia
Phone 81286 0
+ 61 3 9345 2893
Fax 81286 0
+61 3 9498 2010
Email 81286 0
belinda.lee@mh.org.au
Contact person for public queries
Name 81287 0
Dr Roslynn Murphy
Address 81287 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville
VIC 3052
Country 81287 0
Australia
Phone 81287 0
+61393452748
Fax 81287 0
+61 3 9498 2010
Email 81287 0
roslynn.murphy@mh.org.au
Contact person for scientific queries
Name 81288 0
Dr Belinda Lee
Address 81288 0
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville
VIC 3052
Country 81288 0
Australia
Phone 81288 0
+ 61 3 9345 2893
Fax 81288 0
+61 3 9498 2010
Email 81288 0
belinda.lee@mh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD may be collected at a site level. However, IPD will not be made available to the Sponsor. The data that is collected by the Sponsor will not be re-identifiable at the Sponsor level. There are safeguards in place to minimise the risk of a privacy breach. They include analysing the data on an aggregated level and access to the data in a controlled environment with only authorised study personnel. Finally, enabling the availability of IPDs will not help meet the primary and secondary objectives of the study which are dependent on the results from the study population rather than on an individual basis.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AICirculating tumour DNA: a challenging innovation to develop “precision onco-surgery” in pancreatic adenocarcinoma2022https://doi.org/10.1038/s41416-022-01745-2
Dimensions AIClinical Applications of Circulating Tumour DNA in Pancreatic Adenocarcinoma2019https://doi.org/10.3390/jpm9030037
Dimensions AICirculating Tumour DNA to Guide Treatment of Gastrointestinal Malignancies2020https://doi.org/10.1159/000509657
N.B. These documents automatically identified may not have been verified by the study sponsor.