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

Metastatic Pancreatic Cancer Clinical Trial

— SINAI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05363007
• Other study ID #: 202110064MIPB
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: National Taiwan University Hospital
• Contact: Shih-Hung Yang, MD., PhD.
• Phone: 886-2-23123456
• Email: b4401064[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• nanoliposomal irinotecan
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)

Radiation:
• spleen irradiation
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

Locations

Country	Name	City	State
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12W-PFS	12-week PFS rate (%)	12 week