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

Sponsor
National Taiwan University Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05363007
Collaborator
(none)
60
Enrollment
2
Arms
25
Anticipated Duration (Months)

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: nanoliposomal irinotecan
  • Radiation: spleen irradiation
 Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Spleen Irradiation With Nanoliposomal Irinotecan Plus 5-FU and Leucovorin in Metastatic Pancreatic Adenocarcinoma: a Phase II Study (SINAI)
Anticipated Study Start Date :
Jun 1, 2022
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Jun 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Upfront SI

Upfront nanoliposomal irinotecan + 5-FU/leucovorin plus SI

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)
Other Names:
  • 5-FU/leucovorin

    • 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
    Experimental: Add-on SI

    Add-on SI following limited progression to nanoliposomal irinotecan + 5-FU/leucovorin

    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)
    Other Names:
  • 5-FU/leucovorin

    • 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

    Outcome Measures

    Primary Outcome Measures

    1. 12W-PFS [12 week]

      12-week PFS rate (%)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • National Taiwan University Hospital

    Investigators

    • Principal Investigator: Shih-Hung Yang, MD., PhD., National Taiwan University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Taiwan University Hospital
    ClinicalTrials.gov Identifier:
    NCT05363007
    Other Study ID Numbers:
    • 202110064MIPB
    First Posted:
    May 5, 2022
    Last Update Posted:
    May 12, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Keywords provided by National Taiwan University Hospital
    pancreatic cancer
    nanoliposomal irinotecan
    spleen irradiation
    Additional relevant MeSH terms:
    Adenocarcinoma
    Pancreatic Neoplasms
    Leucovorin
    Irinotecan

    Study Results

    No Results Posted as of May 12, 2022