Clinical trial NCT05363007: Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma
Official title: Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma: a Phase II Study (SINAI)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Pancreatic Cancer
Keywords: pancreatic cancer
nanoliposomal irinotecan
spleen irradiation
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2022-05-05
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 12W-PFS
timeFrame: 12 week
Secondary outcomes:
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Shih-Hung Yang, MD., PhD.
role: PRINCIPAL_INVESTIGATOR
References: