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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Recurrent Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Radiation: Additional stereotactic body radiation therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Trials within Cohorts (TwiCs)
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic body radiation therapy