Neoadjuvant Stereotactic Ablative Radiotherapy for Pancreatic Ductal Adenocarcinoma

NCT04915417 | Unknown DMC

• 1 other identifier: 118543
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pancreatic cancer (PC) is expected to be the third leading cause of cancer death in Canada in 2019 \[1\]. Localized pancreatic cancer may be classified as resectable, borderline resectable, or locally advanced. To date, radical surgical resection and adjuvant treatment provide the greatest chance of long-term disease control and overall survival \[2,3\]. Despite this favourable group, the five-year survival rates are approximately 20% \[4\]. Neoadjuvant therapy (NAT) for resectable pancreatic cancer (RPC) has been widely accepted for the management of borderline resectable PC (BRPC) to increase the likelihood of achieving R0 resection \[4-7\]. However, to date, NAT for RPC is still an area of debate due to the lack of large prospective randomized controlled trials that compare this technique to surgery plus adjuvant therapy. Stereotactic ablative radiation therapy (SABR) uses modern radiotherapy planning and targeting technologies to precisely deliver larger, ablative doses of radiotherapy in 1-8 fractions. The role of SABR in RPC has yet to be fully established. The typical goal of radiation therapy in the neoadjuvant setting is to improve local control and increase R0 resection rates. However, there are still concerns about the timing of surgery after SABR and any implementation should be evaluated for safety. Treatments inherently changes the tumour and can cause immunomodulatory effects. SABR has anti-neoplastic effects both directly on the tumour and by its interactions with the immune system. In addition to the direct DNA damage, it is felt that SABR also increases T-cell priming, antigen production and presentation. Pancreatic cancer's dense, collagen rich stroma has prevented patients from receiving the same benefits of checkpoint inhibition that have been achieved in other cancer sites.

Conditions

Resectable Pancreatic Adenocarcinoma; Borderline Resectable Pancreatic Adenocarcinoma

Keywords

Stereotactic Ablative Body Radiation Therapy; Neoadjuvant; Pancreatic Adenocarcinoma; Hybrid PET/MRI; CT Perfusion; Blood Proteomics; Immunomodulation

Outcome Measures

Primary Outcomes (2)

• Toxicity of Neoadjuvant SABR

  Patients will be evaluated for toxicity during their follow-up exams according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  2 years

• Quality of Life (QOL)

  QOL will be measured using the Functional Assessment of Cancer Therapy for Hepatobiliary and Pancreatic Subscale (FACT-Hep HCS)

  2 years

Secondary Outcomes (16)

• Change in tumor blood flow assessed by dynamic contrast enhanced CT imaging

  <2 weeks after completion of chemotherapy (Arm 2 only)

• Change in tumor blood flow assessed by dynamic contrast enhanced CT imaging

  <6 hours after first fraction of radiation therapy (Arm 1 only)

• Change in tumor blood flow assessed by dynamic contrast enhanced CT imaging

  <6 hours after first fraction of radiation therapy (Arm 2 only)

• Change in tumor blood flow assessed by dynamic contrast enhanced CT imaging

  2-4 weeks after radiation completed (Arm 1 only)

• Change in tumor blood flow assessed by dynamic contrast enhanced CT imaging

  2-4 weeks after radiation completed (Arm 2 only)

Study Arms (2)

Resectable Pancreatic Ductal Adenocarcinoma (PDAC)

EXPERIMENTAL

10 Resectable PDAC patients will receive a hybrid PET/MRI before SABR and DCE-CT before SABR, 6 hours after the first SABR fraction, and 4 weeks after the last fraction of SABR (before surgery)

Radiation: Stereotactic Ablative Body Radiotherapy (SABR)

Borderline Resectable Pancreatic Ductal Adenocarcinoma (PDAC)

EXPERIMENTAL

20 Borderline Resectable PDAC patients will receive a DCE-CT scan prior to neoadjuvant chemotherapy, a PET/MRI and DCE-CT after neoadjuvant chemotherapy and before SABR, DCE-CT at 6 hours after the first SABR fraction, and 4 weeks after the last fraction of SABR (before surgery)

Radiation: Stereotactic Ablative Body Radiotherapy (SABR)

Interventions

Stereotactic Ablative Body Radiotherapy (SABR) RADIATION

Patients will receive 27-30 Gy in 3 fractions to the planning target volume (PTV) with a simultaneous in-field boost to the metabolically active areas of the gross tumor volume (GTV) to a maximum of 45 Gy. Patients will be treated every other day.

Borderline Resectable Pancreatic Ductal Adenocarcinoma (PDAC); Resectable Pancreatic Ductal Adenocarcinoma (PDAC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older
• Able to provide informed consent
• Histologically confirmed primary pancreatic cancer, or willing to undergo endoscopic ultrasound (EUS) with synchronous fiducial marker placement and biopsy
• No evidence of distant metastases (M0)
• Medically fit to undergo surgical resection
• Life expectancy \>6 months
• Adequate renal function to tolerate contrast dye for imaging
• Upfront resectable pancreatic cancer
• No evidence of nodal disease (N0)
• Appropriate to undergo a pancreaticoduodenectomy within 4-6 weeks of registration
• Borderline resectable or upfront resectable pancreatic cancer
• Plan for surgical resection independent of the biochemical or radiographic response to SABR

You may not qualify if:

• Serious medical comorbidities or other contraindications to radiotherapy or surgery
• Gross disease involving duodenum or stomach
• Unable to have fiducials placed.
• Recurrent pancreatic cancer
• Prior abdominal radiation at any time
• Inability to attend full course of radiotherapy, surgery, or follow-up visits
• Contrast allergy
• Pregnant or lactating women
• Receipt of any neoadjuvant system therapy, standard cytotoxic therapy or experimental
• Elevated bilirubin or liver enzymes considered to be a contraindication to irinotecan chemotherapy, unless an intervention is planned to improve hepatic functioning

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• London Health Sciences Foundation: collaborator

Central Study Contacts

Stewart Gaede

CONTACT

5196858605; stewart.gaede@lhsc.on.ca

Danielle Porplycia

CONTACT

5196858600; danielle.porplycia@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 7, 2021
• Study Start: August 1, 2021
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2024
• Last Updated: June 22, 2021

Record last verified: 2021-05