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A randomized phase II study of second line treatment with liposomal irinotecan and S1 versus liposomal irinotecan and 5-fluorouracil in patients with metastatic pancreatic cancer who failed on first line gemcitabine-based chemotherapy

Phase 2
Active, not recruiting
Conditions
metastatic pancreatic cancer
Registration Number
2023-509463-24-01
Lead Sponsor
Amsterdam UMC
Brief Summary

To determine the progression free survival (PFS) benefit of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma, or progression within 6 months of adjuvant gemcitabine treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruitment ended
Sex
Not specified
Target Recruitment
146
Inclusion Criteria

Able to understand and provide written informed consent

≥ 18 years of age

Histologically or cytologically confirmed adenocarcinoma of pancreas

Documented metastatic disease, according to RECIST 1.1.

Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment

Adequate hepatic (serum bilirubin total between 0-17 μmol/L, AST between 0-40 U/L, ALT between 0-34 U/L, renal (creatinine between 65-95 μmol/L) and hematological (hemoglobin between 7.5-10 mmol/L, platelets between 150-400 10E9/L, leukocytes between 4.0-10.5 10E9/L) function

Exclusion Criteria

Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)

Current use or any use in last two weeks of strong CYP2A6- enzyme inhibitors, CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors

Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.

Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)

Previous treatment with fluoropyrimidine therapy

Known dihydropyrimidine dehydrogenase (DPD) deficiency

Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of liposomal irinotecan (Nal-IRI).

or male patients: unwilling to use contraception during treatment and 4 months following last dose of Nal-IRI and 6 months after S-1

Contraception required for 6 months following the last dose of S-1

Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.

Severe renal impairment (CLcr ≤ 30 ml/min)

Inadequate bone marrow reserves as evidenced by: a. ANC ≤ 1,5 x 10 9 /L; or b. Platelet count ≤ 100 x 10 9 /L;

WHO/PS 2 or higher

Any clinically significant disorder impacting the risk-benefit balance negatively per physician’s judgment

Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1

Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months

NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings

Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Progression free survival

Progression free survival

Secondary Outcome Measures
NameTimeMethod
Overall survival

Overall survival

Response rate according to RECIST 1.1

Response rate according to RECIST 1.1

Adverse events according to NCI CTC version 4.0

Adverse events according to NCI CTC version 4.0

Quality of life (QLQ-C30)

Quality of life (QLQ-C30)

Trial Locations

Locations (5)

Centro Ricerche Cliniche Di Verona S.r.l.

🇮🇹

Verona, Italy

Amsterdam UMC Stichting

🇳🇱

Amsterdam, Netherlands

Academisch Ziekenhuis Maastricht

🇳🇱

Maastricht, Netherlands

Vall D Hebron Institute Of Oncology

🇪🇸

Barcelona, Spain

Medical University Of Vienna

🇦🇹

Vienna, Austria

Centro Ricerche Cliniche Di Verona S.r.l.
🇮🇹Verona, Italy
Davide Melisi
Site contact
+39458121111
ufficio.protocollo@aovr.veneto.it

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