DYNAMIC-Pancreas
  • DYNAMIC-Pancreas
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Trial Status

In Follow-up

Cancer Type

Pancreatic Cancer

Protocol Title

Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer: A Multicentre Randomised Study (DYNAMIC-Pancreas)

Purpose of the Study

Pancreatic cancer is an aggressive disease with few long term survivors.  The poor outlook for patients diagnosed with pancreatic cancer is associated with the difficulty to detect pancreatic cancer at an early stage and poor response to chemotherapy and radiotherapy.  A biomarker that can inform clinicians of a patient’s risk of disease recurrence and guide treatment decisions would have a major impact on the management of pancreatic cancer – ctDNA may act as one such biomarker.

Eligibility Criteria

Inclusion Criteria

  1. Subjects who have undergone complete macroscopic resection for adenocarcinoma of the pancreas 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 –
  8. Fully informed written consent given

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: Moderate/severe renal impairment, Absolute neutrophil count <1.0×109/L, Platelet count <75×109/L, Haemoglobin <80 g/L, 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.

Email Contact

DYNAMIC-P@mh.org.au

Study Chairs

Dr Belinda Lee
Associate Professor Jeanne Tie
Professor Peter Gibbs

DETAILED INFORMATION AVAILABLE

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) please click here.

Funding

The Marcus Foundation

Trial Status

In Follow-up

Cancer Type

Pancreatic Cancer

Protocol Title

Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Early Stage Pancreatic Cancer: A Multicentre Randomised Study (DYNAMIC-Pancreas)

AIM

Primary Objective:

  • To demonstrate that a ctDNA-informed adjuvant therapy approach following curative intent surgery for localised pancreatic cancer could reduce the proportion of patients, compared to standard of care treatment, that have detectable ctDNA after completing adjuvant therapy

Secondary Objectives:

  • To explore if a ctDNA-informed adjuvant therapy approach could improve recurrence free survival compared to standard of care
  • To explore if a ctDNA-informed adjuvant therapy approach could improve overall survival compared to standard of care
  • To correlate post-operative ctDNA results with recurrence-free and overall survival
  • To correlate end of treatment ctDNA results with recurrence-free and overall survival

Exploratory Objectives

  • To demonstrate the feasibility of an adjuvant chemotherapy strategy (treatment de-escalation or escalation) based on post-operative ctDNA results.
  • To explore if a ctDNA-informed adjuvant therapy approach could reduce the duration and/or intensity of chemotherapy use compared to standard of care for selected patients, without compromising survival outcomes
  • To explore the health economic impact of a ctDNA-informed adjuvant therapy approach compared to standard of care

Background

Pancreatic cancer is an aggressive disease. It carries a poor prognosis which is in part related to the inability to detect pancreatic cancer at an early stage, the potential for early spread and its poor sensitivity to chemotherapy or radiotherapy. Pancreatic cancer is predicted to be the second leading cause of cancer-related deaths by 2020. Currently, long-term survival can only be achieved with surgical resection of localised disease but relapse rates are as high as 80-85% despite “curative” resection. Adjuvant therapy can reduce the rate of relapse and is recommended for patients undergoing surgical resection for curative intent.   The high rate of relapse following potentially curative surgery highlights the need for better strategies to inform treatment. The use of a biomarker, circulating tumour DNA (ctDNA), could be one such strategy.

Patients with positive ctDNA results following surgery would be defined as having a high risk of relapse. For these patients, adjuvant chemotherapy would be escalated to a more intensive therapy. Conversely, patients with negative post-op ctDNA would be spared the toxicity associated with more aggressive combination regimens, with minimal to no risk of compromising survival outcome.

The major driver of this study is to demonstrate that a ctDNA-directed approach to adjuvant chemotherapy for patients with early stage pancreatic cancer could lead to significant gains in preventing recurrence through treatment escalation, ultimately improving survival. However, also of great importance is the potential of a ctDNA-directed approach to reduce unnecessary treatment (treatment de-escalation) in low risk patients, reducing treatment related toxicity, and direct and indirect treatment related costs.

CLINICAL TRIAL DESIGN

Patients will be randomised 1:1 into either a non-biomarker driven, standard of care (SOC) adjuvant treatment arm (Cohort A) or a ctDNA informed biomarker driven arm (cohort B), where treatment will be determined by the ctDNA results after surgery (i.e Cohort B1– ctDNA informed, biomarker negative; Cohort B2 – ctDNA informed, biomarker positive).

In Cohort A, patients will receive standard of care chemotherapy.  In the biomarker driven arms Cohort B1 & B2, treatment will be offered according to the ctDNA result. Patients who are “ctDNA-negative” will be treated with a de-escalated treatment strategy.  Patients in the biomarker driven arm who are “ctDNA-positive” will be treated with an escalation chemotherapy strategy involving either triplet therapy (fluoropyrimidine, irinotecan and oxaliplatin) FOLFIRINOX OR gemcitabine plus nab-paclitaxel (Abraxane).

Patients Recruited

Click to access the table and view recruitment data on all AGITG open trials:

Open Trial Recruitment Table

Contact Email

DYNAMIC-P@mh.org.au

Principal Investigators

Professor Peter Gibbs

Associate Professor Jeanne Tie
Dr Belinda Lee

Detailed Information Available on

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here.

Funding

The Marcus Foundation