MR-Guided Adaptive SBRT of Primary Tumor for Pain Control in Metastatic PDAC

Study Overview
=================
Brief Summary
-----------------
The MASPAC trial investigates the added benefit of MR-guided adaptive SBRT of the primary tumor embedded between standard chemotherapy cycles for pain control and prevention of pain in patients with metastatic PDAC (mPDAC).

Detailed Description
-----------------
Patients not progressing after 8 weeks of standard of care systemic therapy (SoC-CT: minimum doublet chemotherapy) will be included and randomized between arm A, receiving MR-guided adaptive SBRT of the primary tumor combined with continuation of SoC-CT, and arm B, continuing SoC-CT without SBRT. Arm A: The primary tumor is treated with SBRT (6.6 Gy x 5) on a MR-LINAC in breath-hold technique. This scheme was shown to have a reasonable toxicity profile on a conventional LINAC. A low toxicity profile is even more important in patients with metastatic and therefore definitively incurable cancer. Therefore, treatment is performed on a MR-LINAC to deliver high doses to the tumor while keeping the toxicity profile as low as possible. For this purpose, daily adaptive planning is performed aiming to maintain stringent dose constraints for organs at risk (duodenum / stomach / bowel / kidney). Chemotherapy will be continued after SBRT. Arm B: Continuing SoC-CT (according to clinical routine appr. 2 weeks after the previous cycle) without SBRT.

Official Title
-----------------
MR-Guided Adaptive Stereotactic Body Radiotherapy (SBRT) of Primary Tumor for Pain Control in Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) - a Randomized, Controlled Clinical Study

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Radiation: SBRT
* Drug: SOC chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients with histologically proven, metastatic pancreatic adenocarcinoma of the pancreatic head or body amenable for MR-guided adaptive SBRT with at least stable disease after 8 weeks of standard of care doublet chemotherapy age >18 years Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 Ability to follow study instructions and likely to attend and complete all required visits Exclusion Criteria: Subjects not able to give consent Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical study Simultaneous participation in another clinical study or participation in any clinical trial involving an investigational medicinal product or treatment within 30 days prior to beginning of this study Subjects with a physical or psychiatric condition which at the investigator's discretion may put the subject at risk, may confound the study results, or may interfere with the subject's participation in this study Women of child bearing potential or sexually active males not willing to use effective contraception while on treatment and 12 weeks after the end of treatment (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases Biopsy proven tumor invasion into the stomach and/or duodenum Medically uncontrolled pain

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: SBRT<br>mPDAC patients not progressing after 8 weeks of standard of care systemic therapy (SoC-CT: minimum doublet chemotherapy). The primary tumor is treated with SBRT (6.6Gy x 5) on a MR-LINAC in breath-hold technique. For this purpose, daily adaptive planning is performed aiming to maintain stringent dose constraints for organs at risk (duodenum / stomach / bowel / kidney). Chemotherapy will be continued after SBRT. | Radiation: SBRT<br>* online adaptive MR-guided hypofractionated stereotactic radiotherapy<br>* Other names: oMRgRT;Drug: SOC chemotherapy<br>* The chemotherapy is given according to current standard of care, consisting of in minimum doublet - chemotherapy and excluding monotherapy regimens.<br>|
| Active Comparator: Arm B: SOC<br>Continuing SoC-CT (according to clinical routine appr. 2 weeks after the previous cycle) without SBRT. | Drug: SOC chemotherapy<br>* The chemotherapy is given according to current standard of care, consisting of in minimum doublet - chemotherapy and excluding monotherapy regimens.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean cumulative pain index | Mean Cumulative pain index: AUC of pain scores rated every 4 weeks until death or end of study using numeric rating scale (NRS, 0= no pain, 10 = worst pain) divided by number of multiples of 4 weeks since randomization | through study completion, at least 24 weeks or until death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of biliary complications | Biliary complications defined as cholangitis or post-hepatic cholestasis requiring drainage | through study completion, at least 24 weeks or until death | 
| Malnutrition | Nutritional status measuring bioimpedance-derived phase angle (BIA) every 12 weeks | through study completion, at least 24 weeks or until death | 
| Treatment toxicity | Treatment toxicity according to CTCAE v5.0 | through study completion, at least 24 weeks or until death | 
| Death from any cause |  | through study completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metastatic pancreatic cancer, SBRT, MR linac, chemotherapy, pain control