Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma

Study Overview
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Brief Summary
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Splenomegaly is common in advanced pancreatic ductal adenocarcinoma (PDAC). The spleen is an important source of immune suppressive cells and phagocytic cells and may mediate the accumulation of liposomal drugs and immunosuppression. In this study, spleen irradiation (SI) will be added to standard chemotherapy.

Detailed Description
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Splenomegaly is common in PDAC. Therefore, we design a phase II study to enroll metastatic PDAC patients who have failed prior gemcitabine-based therapy and have splenomegaly. With add-on SI to standard nal-IRI/FL therapy, we hypothesize that 1) splenic phagocytes and spleen volume will be reduced with attenuated entrapment of nal-IRI within spleen, 2) splenic source of immunosuppressive immune cells will be reduced with potential reconstitution of antitumor TME.

Official Title
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Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma: a Phase II Study (SINAI)

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Drug: nanoliposomal irinotecan
* Radiation: spleen irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Arm A: histologically or cytologically proved PDAC metastatic PDAC failed frontline gemcitabine-based chemotherapy and preparing for application of NHI-reimbursed nal-IRI/FL splenomegaly: SV > 270 ml (estimated) lymphopenia: < 1200/mm3 no previous radiotherapy, local therapy (eg. radiofrequency ablation, irreversible electroporation, etc.), cell therapy (autologous or allogenic) used for pancreatic cancer presence of at least one measurable lesion outside spleen age between 20 and 75 years at registration ECOG performance status of 0 or 1 adequate major organ functions Arm B: limited progressive disease after prior nal-IRI/FL prior treatment of nal-IRI/FL at least 4 doses histologically or cytologically proven PDAC metastatic PDAC before starting prior nal-IRI/FL failed frontline gemcitabine-based chemotherapy before prior nal-IRI/FL presence of at least one measurable lesion outside spleen age between 20 and 75 years at registration ECOG performance status of 0 or 1 or 2 after the chemotherapy phase adequate major organ functions Exclusion Criteria: interstitial lung disease presence of diarrhea ≥ CTCAE v.5.0 grade 2 concomitant systemic infection requiring treatment clinically significant co-morbid medical conditions prior organ allograft or allogeneic bone marrow transplantation received systemic corticosteroids or immunosuppressants within 28 days before registration known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome moderate or severe ascites, pleural effusion, or pericardial effusion requiring treatment central nervous system metastasis prior or concurrent malignancies within the last 3 years, with the exception of carcinoma in situ of the cervix, or basal type skin cancer any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury. pregnant women or nursing mothers, or positive pregnancy tests severe mental disorder spleen metastasis or direct invasion

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upfront SI<br>Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI | Drug: nanoliposomal irinotecan<br>* Upfront SI (Arm A): Upfront nanoliposomal irinotecan (80 mg/m2, day 1) + 5-FU/leucovorin (2400 mg/m2, 400 mg/m2) plus SI Add-on SI (Arm B): Add-on SI following limited progression to prior nanoliposomal irinotecan (last dose used) + 5-FU/leucovorin (last dose used)<br>* Other names: 5-FU/leucovorin;Radiation: spleen irradiation<br>* Upfront SI (Arm A): upfront spleen irradiation (1 Gy/fx, day 1-4) in cycle 2 Add-on SI (Arm B): add-on spleen irradiation (1 Gy/fx, day 1-4) in cycle 1 following limited progression to prior nanoliposomal irinotecan + 5-FU/leucovorin<br>|
| Experimental: Add-on SI<br>Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin | Drug: nanoliposomal irinotecan<br>* Upfront SI (Arm A): Upfront nanoliposomal irinotecan (80 mg/m2, day 1) + 5-FU/leucovorin (2400 mg/m2, 400 mg/m2) plus SI Add-on SI (Arm B): Add-on SI following limited progression to prior nanoliposomal irinotecan (last dose used) + 5-FU/leucovorin (last dose used)<br>* Other names: 5-FU/leucovorin;Radiation: spleen irradiation<br>* Upfront SI (Arm A): upfront spleen irradiation (1 Gy/fx, day 1-4) in cycle 2 Add-on SI (Arm B): add-on spleen irradiation (1 Gy/fx, day 1-4) in cycle 1 following limited progression to prior nanoliposomal irinotecan + 5-FU/leucovorin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12W-PFS | 12-week PFS rate (%) | 12 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, nanoliposomal irinotecan, spleen irradiation