A Phase I open label followed by a Phase II randomized, controlled study to assess the efficacy and safety of ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic pancreatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ability Pharmaceuticals S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Aug 2020 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515379-36-00

EudraCT number

2020-002791-13

ClinicalTrials.gov

NCT04431258

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

- For Phase I: Safety of ABTL0812 plus FOLFIRINOX.

- For Phase II: To determine the efficacy of ABTL0812 in combination with FOLFIRINOX vs. FOLFIRINOX plus placebo by progression free survival (PFS) according to central review.

Secondary objectives 10

1. Phase I: To determine the efficacy of ABTL0812 in combination with FOLFIRINOX
2. Phase I: Pharmacokinetics of ABTL0812
3. Phase I: Pharmacodynamic biomarkers
4. Phase II: To determine the efficacy of ABTL0812 in combination with FOLFIRINOX vs. FOLFIRINOX plus placebo
5. Phase II: To determine the safety and tolerability of ABTL0812 plus FOLFIRINOX
6. Phase II: Pharmacokinetics and relative bioequivalence of ABTL0812
7. Phase II: Pharmacodynamic biomarkers
8. Phase II: Quality of life
9. Phase II: Predictive biomarkers of treatment response in solid and liquid tumor biopsies
10. Phase II: Prognostic biomarkers in blood

Conditions and MedDRA coding

Metastatic pancreatic ductal adenocarcinoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Histologically or cytologically confirmed carcinoma, adenocarcinoma or ductal adenocarcinoma of the pancreas.
2. Confirmed metastatic disease.
3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines with at least one “target lesion” to be used to assess response. Tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
5. Age, older than 18 years old.
6. For Spain. Adequate hematologic function, measured as: absolute neutrophil count ≥ 1.5x10^9/L, platelet count ≥ 100x10^9/L without transfusion support and hemoglobin ≥ 10 g/dL.
7. For France. Adequate hematologic function, measured as: absolute neutrophil count ≥ 2.0x10^9/L, platelet count ≥ 100x10^9/L without transfusion support and hemoglobin ≥ 10 g/dL.
8. Total bilirubin ≤ 1.5 x ULN.
9. Albumin ≥ 3.3 g/dL.
10. AST (SGOT) and ALT (SGPT) ≤ 2.5 times x upper limit of normal (≤ 5 times the ULN in patients with evidence of liver metastases).
11. Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of liver metastases).
12. Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2.
13. Only for Phase II patients. If available, a sample of tumor tissue or cytology (either archival or new tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample should be provided.
14. For Spain. Contraception: All premenopausal female patients must use contraception. Male patients and their female partners (if fertile), must use contraception as well. In both cases, contraception means two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug.
15. For France. Contraception: All premenopausal female patients must use contraception. Male patients and their female partners (if fertile), must use contraception as well. Contraception means two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug, and female patient should extend contraception measures up to 9 months of last chemotherapy session with oxaliplatin.
16. Willing and able to provide informed consent.
17. Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol.

Exclusion criteria 13

1. Patients with any histology other than carcinoma, adenocarcinoma or ductal adenocarcinoma (such as squamous cell, acinar cell, medullary, colloid, neuroendocrine, etc).
2. Patients has only locally advanced disease, resectable or borderline resectable.
3. The patient has received chemotherapy as adjuvant therapy for locally advanced disease, resectable or borderline resectable.
4. Patient has received previous abdominal radiotherapy, (with the exception of analgesic radiotherapy that was not performed on target lesions).
5. Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway by a systemic route.
6. History of chronic diarrhea or inflammatory disease of the colon or rectum, or occlusion or sub-occlusion not resolved under symptomatic treatment.
7. Patient is pregnant or in lactation period. High sensitivity pregnancy test (urine or serum) to be performed within 7 days before study treatment starts.
8. Patient had myocardial infarction within ≤ 6 months prior to study entry, LVEF <50%, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication.
9. 12-lead ECG with clinically relevant abnormality or showing a QTcF >450 ms, PR >210 ms, or QRS >120 ms at screening.
10. Patients with any other medical conditions (such as psychiatric illness, cardiovascular disease, infectious diseases, abnormal physical examination or laboratory findings) that in the opinion of the investigator may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
11. Patient has active Hepatitis B or C, human immunodeficiency virus (HIV) or Covid-19 infection with non-controlled disease according to the treating physician.
12. For France. Patients with complete absence of dihydropyrimidine dehydrogenase (DPD), defined as blood uracil level ≥150 ng/ml.
13. Patients unable to provide informed consent like those under administrative or legal supervision.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX
2. Phase II: PFS using RECIST v1.1 by central review

Secondary endpoints 21

1. Phase I: PFS using RECIST v1.1 by investigator analysis
2. Phase I: Objective response rate (ORR)
3. Phase I: PFS at 6 months
4. Phase I: Pharmacokinetic analysis of plasma samples
5. Phase I: Analysis of TRIB3 and CHOP in blood samples. Additional biomarkers might be included
6. Phase II: PFS using RECIST v1.1 by investigator analysis
7. Phase II: Objective response rate (ORR)
8. Phase II: PFS at 6 months
9. Phase II: Time to second objective disease progression (PFS2)
10. Phase II: Time to response (TTR)
11. Phase II: Duration of response (DOR)
12. Phase II: Overall survival (OS)
13. Phase II: OS at 1 year
14. Phase II: Disease control rate (DCR) at 16 weeks by central review and investigator analysis
15. Phase II: Time to first subsequent therapy or death (TFST)
16. Phase II: Adverse Events (AE) physical examination, vital signs and laboratory findings according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0
17. Phase II: Pharmacokinetic analysis of plasma samples after capsules and oral solution
18. Phase II: Analysis of TRIB3 and CHOP in blood samples. Additional biomarkers might be included
19. Phase II: Questionnaires QLQ-C30 and QLQ-PAN26 from EORTC
20. Phase II: Analysis of DNA mutations and gene expression in solid and liquid biopsies (plasma)
21. Phase II: Analysis of carbohydrate antigen (CA 19-9) in blood. Additional biomarkers might be included

Investigational products

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

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ability Pharmaceuticals S.A.

Sponsor organisation

Ability Pharmaceuticals S.A.

Address

Avinguda Del Parc Tecnologic 3, Parc Tecnologic Del Valles, Cerdanyola Del Valles Parc Tecnologic Del Valles Cerdanyola Del Valles

City

Barcelona

Postcode

08290

Country

Spain

Scientific contact point

Organisation

Ability Pharmaceuticals S.A.

Contact name

Gemma Fierro

Public contact point

Organisation

Ability Pharmaceuticals S.A.

Contact name

Carles Domenech

Locations

2 EU/EEA countries · 17 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 6 files

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

Application history

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