Exploratory clinical trial to assess safety, tolerability efficacy and pharmacokinetics of CEB-01 PLGA membrane in participants with pancreatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cebiotex S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Aug 2024 → ongoing

Decision date (initial)

2024-06-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Efficacy

To assess the safety and tolerability of CEB-01.

Secondary objectives 2

1. To assess the efficacy of CEB-01 in pancreatic carcinoma.
2. To characterise the pharmacokinetics of SN-38.

Conditions and MedDRA coding

Pancreatic carcinoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

There is no plan to share IPD*

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Age ≥18 years.
2. Neoadjuvant chemotherapy is allowed in borderline and/or locally advanced cases borderline completed at least 4 weeks before surgery.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
4. Female subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at time of screening.
5. Men and women of childbearing potential must be willing to use adequate contraception throughout the study and for 6 months after surgery.
6. Participants diagnosed with: a. Lesion/s of histologically or cytologically confirmed de novo carcinoma, adenocarcinoma or ductal adenocarcinoma of the pancreas with only locally advanced disease, resectable or borderline resectable. b. Histopathological confirmation of the diagnosis can be done during surgery by means of intraoperative biopsy as per clinical practice. No need of preoperative biopsy.
7. Participants previously treated with chemotherapy will be eligible if they have not had documented progressive disease during treatment.
8. Participants must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion obtained by a validate imaging technique (i.e., magnetic resonance imaging (MRI), computed tomography (CT) scan, PET scan, ultrasounds or others) that can be accurately measured.
9. Participants should have surgically removable lesion/s or what they will be submitted to a pancreatoduodenectomy.
10. Normal renal function as defined by biochemical parameters as follows: creatinine ≤2 mg/dl or creatinine clearance ≥ 60 ml/min/1.73 m2.
11. Haematological and cardiac function as defined by biochemical and haematological parameters as follows: haemoglobin (Hb) ≥10 g/dL (with preoperative transfusion), platelets ≥80.000/mm3 with intraoperative transfusion, white blood cells (WBC) ≥3.000/mm3, neutrophil count ≥1.500/mm3.
12. Liver function as defined by biochemical parameters as follows: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 4 times the upper limit of normality [ULN]. Recommended serum bilirubin for eligibility is bilirubin ≤ 10 mg/dl (or equivalent value in μmol/L units). Preoperative biliary drainage to be done according to regular practice in each center. Patients in whom preoperative biliary drainage cannot be performed or biliary drainage was not completely effective, individualized decision to be made when bilirubin is ≥ 10 mg/dl (or equivalent value in μmol/L units).
13. Participants must have fully recovered from the acute toxic effects (Grade 3 or above) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this trial.
14. The participant or a legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained prior to any protocol screening procedures.

Exclusion criteria 13

1. Other malignancies within past 2 years.
2. Other relevant concomitant illnesses.
3. Participants’ status post-allogeneic stem cell transplant are not eligible.
4. R2 resections (macroscopic disease remains after surgery).
5. Patients with homozygous UGT1A1 known to be at risk of increased toxicity with irinotecan and SN-38.
6. Active bacterial, viral or fungal infection.
7. Known history of active human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C or chronic liver disease. Testing is not required in the absence of clinical findings or suspicion.
8. Impossibility of ensuring adequate follow-up.
9. Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
10. Contraindication to computed tomography scan (CT).
11. Major surgery within 14 days prior to starting study drug or still in recovery after experiencing surgical complications; neither tumour biopsy nor central line insertion are considered a major surgery.
12. Participants with disease of any major organ system that would compromise their ability to withstand therapy.
13. Pregnancy or lactation. Pregnant women are excluded from this study; if the patient is a lactating mother, breastfeeding should be discontinued.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Serious and non-serious Adverse Events (AE) according to the most updated version of the Common Terminology Criteria for Adverse Events (CTCAE).
2. International Patient Safety Goals (IPSG) after pancreatic surgery.

Secondary endpoints 4

1. Local recurrence-free survival (LRFS).
2. Progression-free survival (PFS).
3. Overall survival (OS).
4. Pharmacokinetic analysis of multiple plasma samples obtained before and after the implant of CEB-01 to calculate: Area under the concentration-time curve (AUC0-inf), Maximum concentration (Cmax), Time of maximum plasma concentration (Tmax) and Terminal half-life (t1/2) of the active substance SN-38.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cebiotex S.L.

Sponsor organisation

Cebiotex S.L.

Address

Via Laietana 26 Tech Pier 07 Entresuelo

City

Barcelona

Postcode

08003

Country

Spain

Scientific contact point

Organisation

Cebiotex S.L.

Contact name

Antonio Perez

Public contact point

Organisation

Cebiotex S.L.

Contact name

Anna Huguet

Third parties 4

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

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

Documents 9 files

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

Application history

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