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

Phase 2

Recruiting

• Conditions: Metastatic Pancreatic Cancer
• Interventions: Drug: nanoliposomal irinotecan; Radiation: spleen irradiation

• Registration Number: NCT05363007
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2022-05-01
• Study First Submitted: 2022-05-02
• Study First Submitted QC: 2022-05-02
• Study First Posted: 2022-05-05
• Status Verified: 2023-06
• Last Update Submitted: 2023-10-13
• Last Update Posted: 2023-10-16
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Upfront SI	nanoliposomal irinotecan	Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI
Add-on SI	nanoliposomal irinotecan	Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
Add-on SI	spleen irradiation	Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
Upfront SI	spleen irradiation	Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI

Primary Outcome Measures

Name	Time	Method
12W-PFS	12 week	12-week PFS rate (%)

Trial Locations

Locations (2)

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan