Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma (SINAI)
Primary Purpose
Metastatic Pancreatic Cancer
Status
Recruiting
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
nanoliposomal irinotecan
spleen irradiation
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Cancer focused on measuring pancreatic cancer, nanoliposomal irinotecan, spleen irradiation
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
Sites / Locations
- National Cheng Kung University HospitalRecruiting
- National Taiwan University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Upfront SI
Add-on SI
Arm Description
Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI
Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
Outcomes
Primary Outcome Measures
12W-PFS
12-week PFS rate (%)
Secondary Outcome Measures
Full Information
NCT ID
NCT05363007
First Posted
May 2, 2022
Last Updated
October 13, 2023
Sponsor
National Taiwan University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05363007
Brief Title
Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma
Acronym
SINAI
Official Title
Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma: a Phase II Study (SINAI)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Cancer
Keywords
pancreatic cancer, nanoliposomal irinotecan, spleen irradiation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Upfront SI
Arm Type
Experimental
Arm Description
Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI
Arm Title
Add-on SI
Arm Type
Experimental
Arm Description
Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin
Intervention Type
Drug
Intervention Name(s)
nanoliposomal irinotecan
Other Intervention Name(s)
5-FU/leucovorin
Intervention Description
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)
Intervention Type
Radiation
Intervention Name(s)
spleen irradiation
Intervention Description
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
Primary Outcome Measure Information:
Title
12W-PFS
Description
12-week PFS rate (%)
Time Frame
12 week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shih-Hung Yang, MD., PhD.
Phone
886-2-23123456
Email
b4401064@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shih-Hung Yang, MD., PhD.
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan-Shen Shan
Email
ysshan@mail.ncku.edu.tw
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Si-Chen Lin
Phone
02-23123456
Email
123796susu@ntuh.gov.tw
12. IPD Sharing Statement
Plan to Share IPD
No
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Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma
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