Randomized phase II study comparing 5FU/LV+Nal-IRI, gemcitabine+Nab-paclitaxel or a sequential regimen of 2 months 5FU/LV+Nal-IRI followed by two months of gemcitabine+Nab-paclitaxel, in metastatic pancreatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Oct 2024 → ongoing

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518143-38-00

EudraCT number

2017-004309-41

ClinicalTrials.gov

NCT03693677

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

- Compare the progression free survival at 6 months in experimental arms (arm A: Nal-Iri plus 5FU/LV and Nab-Paclitaxel plus Gemcitabine alternatively, arm B: Nal-Iri plus 5FU/LV) VS the reference arm (arm C: Nab-Paclitaxel plus Gemcitabine) according to the RECIST 1.1 criteria

Secondary objectives 10

1. - Progression free survival at 6 months (according to central review)
2. - Best objective response rate
3. - Depth of response
4. - Early tumor shrinkage
5. - Progression free survival (according to the investigator and central review)
6. - Overall survival
7. - Time to treatment failure
8. - Safety
9. - Quality of life (EORTC QLQ-C30)
10. - CA 19-9 and CEA monitoring

Conditions and MedDRA coding

Metastatic pancreatic cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. - Histopathologically or cytologically proven pancreatic adenocarcinoma (on primitive or metastatic lesion)
2. - Metastatic disease at a distance
3. - At least one measurable lesion according RECIST v1.1 criteria
4. - 18 ≤ age ≤ 75 years - Life expectancy >12 weeks - Performance status WHO < 2
5. - No prior chemotherapy: adjuvant chemotherapy by gemcitabine +/- capecitabine is allowed if ended at least 12 months before the inclusion and adjuvant or neo-adjuvant FOLRIFINOX chemotherapy is allowed if ended at least 12 months prior the inclusion
6. - Pain well controlled before the inclusion of the patient
7. - ANC ≥ 1,500 cells/μL (without the use of hematopoietic growth factors); platelet count ≥ 100,000 cells/μL, hemoglobin ≥ 9 g/dL (blood transfusions is permitted for patients with hemoglobin levels below 9 g/dL)
8. - Adequate hepatic function as evidenced by: Serum total bilirubin within normal range for the institution (Serum bilirubin ≤ 1,5 UNL) Biliary drainage allowed for biliary obstruction.
9. - Albumin levels ≥ 3.0 g/dL - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN acceptable if liver metastases were present) - Normal renal function test (creatinine clearance ≥ 50 ml/min)
10. - Normal ECG or ECG without any clinically significant findings
11. - Patient able to understand and sign an informed consent
12. - Females of child-bearing potential are required to test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test.
13. - Both male and female patients of reproductive potential were required to agree to use a reliable method of birth control, during the study and for 7 months following the last dose of study drug.
14. - Patient affiliated to social security - Regular follow-up possible

Exclusion criteria 17

1. - Uncontrolled brain or meningeal metastasis, or bone metastasis (no need of systematic CT scan)
2. - Prior radiation therapy (except if there is at least one measurable target outside irradiation area)
3. - Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > Grade 1
4. - History of chronic inflammatory bowel disease
5. - Other types of pancreatic tumours, in particular endocrine or acinar cell tumours
6. - Ampulloma - Gilbert's syndrome
7. - Presence of neuropathy > grade 1 according to NCI-CTC
8. - History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they had been continuously disease free for at least 5 years.
9. - Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
10. - NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
11. - Known hypersensitivity to any of the drugs /constituents or non-lipososomal irinotecan
12. - Any other medical or social condition deemed by the investigator to be likely to interfere with a patient’s ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
13. - Use of CYP3A4/UGT1A inducers/inhibitors
14. - Use of strong CYP2C8 inhibitors or inducers, or presence of any other contraindications for nab-paclitaxel or gemcitabine
15. - ILD presence
16. - Partial or complete DPD deficiency (Uracilemia ≥ 16 ng/ml)
17. - Pregnant or breast feeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the rate of patients alive without progression at 6 months after inclusion

Secondary endpoints 9

1. Best Objective Response (BOR): BOR is defined as complete or partial response rate according to scans and RECIST v1.1 criteria over the entire treatment period.
2. Progression free survival (PFS): PFS is defined as the time between the date of randomization and the date of the first radiological and/or clinical progression or the date of death (for whatever reason).
3. Overall survival (OS): OS is defined as the time between the date of randomization and the date of death (whatever the cause).
4. Depth of response: This is defined as the relative difference between the sum of the largest diameters of target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the target lesions at inclusion.
5. Early tumor shrinkage: This is defined as the relative difference between the sum of the largest diameters of target lesions at 8 weeks and this sum at inclusion. Early decrease corresponds to a relative difference of > 20% in RECIST v1.1.
6. Time to treatment failure is defined as the time between the date of randomization and the date of discontinuation of all protocol treatments (regardless of cause) or date last news for patients alive under treatment.
7. Safety: Toxicities are evaluated according to NCI-CTC v4.0.
8. Quality of life (EORTC QLQ-C30): Quality of life will be assessed according to the questionnaire of EORTC QLQ-C30
9. Evolution of tumoral markers: The evolution of the markers will be analysed by a graphical representation at each time points of the percentage change from baseline.

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon Cedex

Postcode

21001

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

JULIEN TAIEB

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

JULIEN TAIEB

Locations

1 EU/EEA country · 3 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 11 files

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

Application history

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