Additional Treatment for Isolated Local Pancreatic Cancer Recurrence Using Stereotactic Body Radiation Therapy (ARCADE)

A Randomized Controlled Trial on Additional Treatment for Isolated Local Pancreatic Cancer Recurrence Using Stereotactic Body Radiation Therapy

A randomized controlled trial, nested within an existing prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the 'trials within cohorts' (TwiCs) design in which the effect of additional local ablative therapy compared to current standard of care alone, on survival after recurrence in patients with isolated local pancreatic ductal adenocarcinoma (PDAC) recurrence. The most important secondary endpoint is quality of life. Other secondary endpoints are treatment response, acute and late toxicity, overall survival, progression-free survival, local progression-free survival, distant metastases free survival and reasons for non-eligibility or exclusion.

Study Overview

• Status: Enrolling by invitation
• Conditions: Recurrent Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Radiation: Additional stereotactic body radiation therapy

Detailed Description

Rationale: Disease recurrence remains the main cause of mortality in patients who underwent resection for PDAC. In case of recurrence, patients are currently treated with palliative chemotherapy or best supportive care. In 20-30% of all patients, isolated local PDAC recurrence occurs after resection, which is frequently associated with considerable morbidity from local destructive tumor growth. Although survival after recurrence is predominantly determined by systemic disease, additional local ablative therapy might be of value to improve local disease control in these patients, which could positively affect survival and quality of life (QoL). Previously, radiation therapy has played only a minor role in the treatment of PDAC. As the pancreas is tightly surrounded by organs with limited radiation dose tolerance and subjected to abdominal motion due to respiration and peristalsis, optimal dose delivery has been impeded with conventional radiotherapy techniques. The development of image-guided stereotactic body radiation therapy (SBRT) techniques, however, enabled safe delivery of high irradiation doses to pancreatic lesions. Early retrospective studies have suggested that SBRT might lead to improved local control in patients with isolated local PDAC recurrence, potentially having a beneficial effect on both survival and QoL. In the current, multicenter randomized controlled trial, the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence is compared to standard of care alone, with regard to both survival and quality of life outcomes.

Objective: The main objective of this study is to improve survival after recurrence in patients with isolated local PDAC recurrence using local ablative treatment with SBRT in addition to standard of care. Furthermore, the effects of additional SBRT on QoL will be evaluated within this study.

Study design: A randomized controlled trial, nested within a prospective cohort (PACAP) according to the TwiCs design.

Study population: PACAP-participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies.

Intervention: Local ablative therapy (5 times 8 Gray SBRT) in addition to standard of care.

Comparison: standard of care.

Main study endpoints: The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life. Other secondary endpoints are radiological treatment response, acute and late toxicity, overall, progression-free, local progression-free and distant metastasis free survival and reasons for non-eligibility or exclusion.

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Amsterdam University Medical Center, VUmc
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Erasmus University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participation in the PACAP cohort with written informed consent for being randomized in future studies
• Isolated local recurrence after primary PDAC resection
• Minimum age of 18 years

Exclusion Criteria:

• Distant metastases
• Expected lifespan < 3 months
• Ineligibility for MRI or CT according to the protocol of the local radiology department;
• Highly selective cases with resectable, isolated local recurrence without the need for either systemic or local ablative induction therapy, eligible for re-resection according to the expert panel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Additional stereotactic body radiation therapy; SBRT in addition to standard of care.	Radiation: Additional stereotactic body radiation therapy; 5 fractions of 8 Gray stereotactic body radiation therapy in addition to standard of care.
No Intervention: Standard of care; Treatment according to current clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival after recurrence	The interval between the date of PDAC recurrence diagnosis and either death from any cause or last follow-up.	From the date of PDAC recurrence diagnosis until either death from any cause or last follow-u, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient reported Quality of Life as assessed using Exocrine Pancreatic Insufficiency (EPI) questionnaire	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported non-disease specific health-related Quality of Life (HRQoL) as assessed using the EQ-5D-5L	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported cancer-specific HRQoL as assessed using the EORTC QLQ-C30	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported tumor-specific HRQoL as assessed using the EORTC LQPAN26	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported chemotherapy-induced peripheral neuropathy as assessed using the EORTC QLQ-CIPN20	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported Quality of Life as assessed using the happiness, hospital, anxiety and depression scale (HADS)	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Patient reported Quality of Life as assessed using the worry of progression of cancer scale (WOPS)	Part of the Patient Reported Outcome Measures (PROMs) that are being standardly measured in PACAP-participants.	At baseline and at 3, 6, 9, 12, 18 and 24 months and every subsequent year after enrollment in the PACAP-cohort. Assessed through study completion, up to 18 months
Treatment response assessed on CT-imaging (graded according to RECIST guidelines)	Response to SBRT treatment.	During and immediately after the intervention (SBRT treatment)
Acute and late toxicity of SBRT as assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Assessed during regular follow-up moments. In the intervention arm acute toxicity will be monitored by the treating radiation oncologist. Acute toxicity will be defined as toxicity within 90 days from the end of SBRT treatment and will be assessed in week 1, 3, 6 and 12. Late toxicity is defined as toxicity occurring > 90 days from SBRT.	Through study completion, an average of 18 months
Overall survival	The interval between the date of primary resection and the date of death from any cause or last follow-up.	From the date of primary resection until the date of death from any cause or last follow-up, whichever came first, assessed up to 18 months
Progression-free survival	The interval between the date of disease recurrence and the date that local and/or distant progression of disease occurs.	From the date of disease recurrence until the date that local and/or distant progression of disease occurs, assessed up to 18 months
Local progression-free survival	The interval between the date of disease recurrence and the date that locoregional progression of disease occurs.	From the date of disease recurrence until the date that locoregional progression of disease occurs, assessed up to 18 months
Distant metastases free survival	The interval between the date of disease recurrence and the date that distant progression of disease occurs.	From the date of disease recurrence until the date that distant progression of disease occurs, assessed up to 18 months
Reasons for non-eligibility or exclusion for SBRT treatment	e.g. poor condition, patients wish, deteriorated condition, age.	At the time the patient is assessed eligible for the intervention. Assessed through the study, up to 18 months

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Dutch Pancreatic Cancer Group (DPCG)
• Investigators: Principal Investigator: I. Q. Molenaar, MD, PhD, Regional Academic Cancer Center Utrecht (RACU); Principal Investigator: M. P.W. Intven, MD, PhD, Regional Academic Cancer Center Utrecht (RACU); Principal Investigator: A. M.E. Bruynzeel, MD, PhD, Amsterdam University Medical Center, VUmc; Principal Investigator: J. Nuyttens, MD, PhD, Erasmus Medical Center; Principal Investigator: M. G.H. Besselink, MD, PhD, Amsterdam University Medical Center, AMC; Principal Investigator: B. Groot Koerkamp, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• van Goor IWJM, Daamen LA, Besselink MG, Bruynzeel AME, Busch OR, Cirkel GA, Groot Koerkamp B, Haj Mohammed N, Heerkens HD, van Laarhoven HWM, Meijer GJ, Nuyttens J, van Santvoort HC, van Tienhoven G, Verkooijen HM, Wilmink JW, Molenaar IQ, Intven MPW; Dutch Pancreatic Cancer Group. A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE). Trials. 2022 Oct 28;23(1):913. doi: 10.1186/s13063-022-06829-1. Erratum In: Trials. 2023 Jan 24;24(1):55.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Stereotactic body radiation therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: NL74336.041.20; 20-805 (Other Identifier: METC Utrecht); 12568 (Other Grant/Funding Number: KWF)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data generated during the ARCADE trial will be made available to other researcher upon request from M.P.W. Intven.
• IPD Sharing Access Criteria: Upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No