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

October 13, 2023 updated by: National Taiwan University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
      • Tainan, Taiwan
      • Taipei, Taiwan
        • Recruiting
        • National Taiwan University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
12W-PFS
Time Frame: 12 week
12-week PFS rate (%)
12 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2022

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

May 2, 2022

First Submitted That Met QC Criteria

May 2, 2022

First Posted (Actual)

May 5, 2022

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 13, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202110064MIPB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe