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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Nov 2019 → ongoing

Decision date (initial)

2024-12-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509463-24-01

EudraCT number

2017-004675-31

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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.

Secondary objectives 7

1. To determine the overall survival (OS) 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.
2. To determine the response rate according to RECIST 1.1 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.
3. To determine the adverse events according to NCI CTC version 4.0 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.
4. To determine Quality of life (QoL) 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.
5. To assess expression of relative abundance of stroma in metastatic tumor tissue and stromal markers, including ADAM12 in metastatic tumor tissue and blood as predictor of response to treatment and survival.
6. To explore, by imaging, the effects of the treatment combination on tumor vascularity, and stromal density.
7. To explore changes in ctDNA.

Conditions and MedDRA coding

metastatic pancreatic cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Able to understand and provide written informed consent
2. ≥ 18 years of age
3. Histologically or cytologically confirmed adenocarcinoma of pancreas
4. Documented metastatic disease, according to RECIST 1.1.
5. Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment
6. 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 18

1. Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
2. Severe renal impairment (CLcr ≤ 30 ml/min)
3. Inadequate bone marrow reserves as evidenced by: a. ANC ≤ 1,5 x 10 9 /L; or b. Platelet count ≤ 100 x 10 9 /L;
4. WHO/PS 2 or higher
5. Any clinically significant disorder impacting the risk-benefit balance negatively per physician’s judgment
6. Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
7. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
8. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
9. Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician’s opinion might compromise the patient’s health
10. Current use or any use in last two weeks of strong CYP2A6- enzyme inhibitors, CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
11. Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
12. Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
13. Previous treatment with fluoropyrimidine therapy
14. Known dihydropyrimidine dehydrogenase (DPD) deficiency
15. 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).
16. or male patients: unwilling to use contraception during treatment and 4 months following last dose of Nal-IRI and 6 months after S-1
17. Contraception required for 6 months following the last dose of S-1
18. Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival

Secondary endpoints 4

1. Overall survival
2. Response rate according to RECIST 1.1
3. Adverse events according to NCI CTC version 4.0
4. Quality of life (QLQ-C30)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

J.W. Wilmink

Public contact point

Organisation

Amsterdam UMC

Contact name

J.W. Wilmink

Locations

4 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications