Ultrasound-enhanced Uptake of Chemotherapy in Patients With Inoperable Pancreatic Ductal Adenocarcinoma

Study Overview
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Brief Summary
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Patients with inoperable pancreatic cancer have extremely poor prognosis with five year survival below 8% in Norway. Life-prolonging chemotherapy has very limited effect, but is the only therapeutic option for these patients. This tumor is characterized by poor uptake and chemoresistance. Toxic effects on healthy tissue restrict doses applied and maintenance of treatment intensity. This severely limits clinical outcome. Increasing the local uptake of chemotherapy has potential benefits for patients in connection to side effects, survival and possible cure. Treatment with Focused Ultrasound (FUS) combined with microbubbles (MBs) is proved promising to improve treatment response in animal and clinical trials. Ultrasound can induce biological effects deep inside the body without surgical intervention. This opens for local delivery of drugs at desired sites. FUS in combination with regular contrast MBs has been reported to influence the delivery of drugs to tumors. In this trial FUS and MB will be applied to locally advanced pancreatic cancers shortly after the administration of conventional chemotherapy. Primary aim of the trial is to investigate whether the effect of the cytostatic drug, measured in tumor volume, can be increased.

Official Title
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Ultrasound-enhanced Uptake of Chemotherapy in Patients With Inoperable Pancreatic Ductal Adenocarcinoma - A Randomized Controlled Trial

Conditions
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Carcinoma, Pancreatic Ductal

Intervention / Treatment
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* Combination Product: SonoVue
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiologically verified stage III or IV PDAC or medically inoperable stage IIB T3 PDAC eligible for 1st line treatment with FOLFIRINOX, Gemcitabine -nab Paclitaxel, or Gemcitabine monotherapy. ECOG 0 - 1 Exclusion Criteria: Known contraindications for SonoVue Hematological bleeding status before experimental treatment: Hb < 8g/dL, trc < 80 x10 superscr 9/l, APTT˃ 45s, INR ˃ 1,5 Pregnancy

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 89 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SonoVue<br>SonoVue + chemotherapy | Combination Product: SonoVue<br>* 1,0 ml SonoVue 8ul/ml dispersion is given 9 times at 3,5 minute intervals 9 times, a total dosage of 9 ml. The experimental treatment lasts for 31,5 minutes every treatment day. Administered by authorized site personnel only<br>Drug: Chemotherapy<br>* FOLFIRINOX Regime according to Norwegian national guidelines<br>|
| Active Comparator: control<br>chemotherapy | Drug: Chemotherapy<br>* FOLFIRINOX Regime according to Norwegian national guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume change of primary tumor | measured by segmented tumor volumes on Computed Tomography of primary PDAC tumor from before treatment (baseline) to after 1 cycle of treatment | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of down-staged tumors from stage III to stage II |  | 8 weeks | 
| Number of down-staged tumors from stage III to stage II |  | 1 year | 
| Rate of reported toxicity | Toxicity reported by patients during structured interview after treatment. Type of side effects and severity according to Common Toxicity Criteria (CTC) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Contrast agent BR, SonoVue, Ultrasonic therapy, Microbubbles