Study to compare 2 chemotherapy, one with Irinotecan liposome injection in addition to combination of chemotherapy and one with standard chemotherapy in patients with pancreatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Bioscience Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 May 2020 → 18 Feb 2025

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518303-21-00

EudraCT number

2018-003585-14

ClinicalTrials.gov

NCT04083235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Pharmacokinetic, Pharmacogenetic, Efficacy, Pharmacodynamic, Safety

The primary objective of this study is to evaluate the efficacy of the regimen of irinotecan liposome injection + oxaliplatin + 5 fluorouracil (5-FU)/leucovorin (LV) versus nab paclitaxel + gemcitabine in improving
overall survival (OS) in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas.

Secondary objectives 3

1. to evaluate progression free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 guidelines
2. to evaluate the overall response rate (ORR) according to RECIST Version 1.1 guidelines
3. to evaluate the safety of this regimen in this patient population.

Conditions and MedDRA coding

Metastatic Pancreatic Adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed Informed Consent Form
2. ≥18 years; Females of child-bearing potential must test negative for pregnancy at the time of screening and must agree to use a highly effective method of birth control; Male subjects must agree to use condoms
3. Histological or cytologically confirmed adenocarcinoma of the pancreas that has not been previously treated in the metastatic setting
4. Initial diagnosis of metastatic disease (as per American Joint Committee on Cancer 8th Edition) ≤6 weeks prior to screening
5. Subject has one or more metastatic lesions measurable by CT scan or MRI according to RECIST Version 1.1 criteria
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and within 7 days prior to randomisation
7. Subject has adequate biological parameters: (a) Absolute neutrophil count ≥2000/mm3 without the use of hemopoietic growth factors within the last 7 days prior to randomisation (b) Platelet count ≥100,000/mm3 (c) Haemoglobin ≥9 g/dL obtained ≤14 days prior to randomisation.
8. Adequate hepatic function: (a) Serum total bilirubin ≤1.5x upper limit of normal (b) Aspartate aminotransferase and alanine aminotransferase ≤2.5x ULN
9. Adequate renal function with a creatinine clearance of >30 mL/min
10. Electrocardiogram without any clinically significant findings
11. Adequate coagulation: prothrombin time and partial thromboplastin time within normal limits (≤1.5 x ULN)
12. No clinically significant abnormalities in urinalysis results
13. Subjects infected with HIV are eligible if they meet all the following criteria: (a) CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications (b) Probable long-term survival with HIV if cancer were not present (c) Stable on a highly active antiretroviral therapy (HAART) regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study (d) HIV is not multi-drug resistant (e) Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication

Exclusion criteria 13

1. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject’s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
2. Unwilling or unable to comply with study procedures and/or study visits, including long-term follow-up for survival.
3. Prior treatment of pancreatic cancer in the metastatic setting with surgery, radiotherapy, chemotherapy or investigational therapy: (a) Palliative radiotherapy is permitted (b) Placement of biliary stent/tube is permitted.
4. Prior treatment of pancreatic adenocarcinoma with chemotherapy in the adjuvant setting, except those where at least 12 months have elapsed since completion of the last dose and no persistent treatment-related toxicities are present.
5. Subject has only localised advanced disease.
6. Documented serum albumin <3 g/dL within 7 days prior to randomisation
7. Known history of central nervous system metastases.
8. Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, diarrhoea > Grade 1, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction.
9. History of any second malignancy in the last 2 years; subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years prior to screening. Subjects who have a concurrent malignancy that is clinically stable and does not require tumour-directed treatment are eligible.
10. Known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or any components of 5-FU, LV or oxaliplatin.
11. Known hypersensitivity to any of the components of nab-paclitaxel or gemcitabine
12. Concurrent illnesses that would be a relative contraindication to trial participation such as active cardiac or liver disease, including: (a) Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before screening (b) High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year prior to screening (c) New York Heart Association Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (d) Known historical or active infection with hepatitis B, or active infection with hepatitis C
13. Active infection or an unexplained fever >38.5°C during screening visits or on the first scheduled day of dosing , which in the investigator’s opinion might compromise the subject’s participation in the study or affect the study outcome.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the overall survival of subjects treated with irinotecan liposome injection +oxaliplatin+5 FU/LV compared to subjects treated with nab paclitaxel+gemcitabine.

Secondary endpoints 3

1. Progression Free Survival
2. Overall Response Rate
3. The secondary efficacy endpoints (PFS and ORR) will only be evaluated if the primary efficacy endpoint demonstrates superiority for irinotecan liposome injection+oxaliplatin+5‑FU/LV over nab-‑ paclitaxel+gemcitabine.

Investigational products

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

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Bioscience Inc.

Sponsor organisation

Ipsen Bioscience Inc.

Address

1 Main Street Ste 7

City

Cambridge

Postcode

02142-1599

Country

United States

Scientific contact point

Organisation

Ipsen Bioscience Inc.

Contact name

Medical Development Director (or Medical Director for GMA studies)

Public contact point

Organisation

Ipsen Bioscience Inc.

Contact name

Ipsen Clinical Study Enquiries

Third parties 7

Locations

1 EU/EEA country · 2 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 15 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