A Study of ABTL0812 in Pancreatic Cancer

NCT03417921 | Suspended Phase 1 DMC

• 1 other identifier: ABT-C6-2017
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized Phase I/II Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Gemcitabine and Nab-paclitaxel in Patients With Advanced Metastatic Pancreatic Cancer at First Line Therapy.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Emergent Adverse Events

  Related Adverse Events as Assessed by CTCAE v4.03

  1 year

Study Arms (2)

ARM A

EXPERIMENTAL

ABTL0812 (starting 1,300 mg tid orally) in combination with gemcitabine and nab-paclitaxel will be administered to patients with pancreatic cancer

Drug: ABTL0812; Drug: Gemcitabine and nab-paclitaxel

ARM B

ACTIVE COMPARATOR

Gemcitabine and nab-paclitaxel will be administered to patients with pancreatic cancer as standard pattern

Drug: Gemcitabine and nab-paclitaxel

Interventions

ABTL0812 DRUG

ABTL0812 in combination with gemcitabine and nab-paclitaxel

ARM A

Gemcitabine and nab-paclitaxel DRUG

Gemcitabine and nab-paclitaxel as standard pattern

ARM A; ARM B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥18 years of age
• Willing and able to provide informed consent
• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol
• Patient has one or more metastatic tumors measurable by CT scan (or MRI, if patient is allergic to CT contrast media).
• Patient has not received previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
• Patient has not received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Adequate hematologic function, measured as:
• absolute neutrophil count ≥ 1.5x109/L
• platelet count ≥ 100x109/L
• hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x ULN
• Albumin ≤ 1.5 x ULN AST (SGOT) ≤ 2.5 times x upper limit of normal (ULN) and ALT (SGPT) \< 2.5 times x upper limit of normal (≤5 times the ULN in patients with evidence of liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of liver metastases)
• Serum creatinine ≤1.5 ULN

You may not qualify if:

• Patients fulfilling the following criteria are eligible for participation in the study:
• Patients ≥18 years of age
• Willing and able to provide informed consent
• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol
• Patient has one or more metastatic tumors measurable by CT scan (or MRI, if patient is allergic to CT contrast media).
• Patient has not received previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
• Patient has not received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Adequate hematologic function, measured as:
• absolute neutrophil count ≥ 1.5x109/L
• platelet count ≥ 100x109/L
• hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x ULN
• Albumin ≤ 1.5 x ULN AST (SGOT) ≤ 2.5 times x upper limit of normal (ULN) and ALT (SGPT) \< 2.5 times x upper limit of normal (≤5 times the ULN in patients with evidence of liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of liver metastases)

Sponsors & Collaborators

• Ability Pharmaceuticals SL: lead
• The Cleveland Clinic: collaborator

Study Sites (1)

Marc Cortal

Barcelona, 08190, Spain

Location

Related Publications (7)

• Erazo T, Lorente M, Lopez-Plana A, Munoz-Guardiola P, Fernandez-Nogueira P, Garcia-Martinez JA, Bragado P, Fuster G, Salazar M, Espadaler J, Hernandez-Losa J, Bayascas JR, Cortal M, Vidal L, Gascon P, Gomez-Ferreria M, Alfon J, Velasco G, Domenech C, Lizcano JM. The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase. Clin Cancer Res. 2016 May 15;22(10):2508-19. doi: 10.1158/1078-0432.CCR-15-1808. Epub 2015 Dec 15.

  PMID: 26671995 BACKGROUND

• Munoz-Guardiola P, Casas J, Megias-Roda E, Sole S, Perez-Montoyo H, Yeste-Velasco M, Erazo T, Dieguez-Martinez N, Espinosa-Gil S, Munoz-Pinedo C, Yoldi G, Abad JL, Segura MF, Moran T, Romeo M, Bosch-Barrera J, Oaknin A, Alfon J, Domenech C, Fabrias G, Velasco G, Lizcano JM. The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells. Autophagy. 2021 Jun;17(6):1349-1366. doi: 10.1080/15548627.2020.1761651. Epub 2020 May 25.

  PMID: 32397857 BACKGROUND

• Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Sole-Sanchez S, Munoz-Guardiola P, Megias-Roda E, Perez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodriguez-Freixinos V, Lizcano JM, Domenech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N. Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer. Gynecol Oncol. 2019 May;153(2):425-435. doi: 10.1016/j.ygyno.2019.03.002. Epub 2019 Mar 7.

  PMID: 30853360 BACKGROUND

• Lopez-Plana A, Fernandez-Nogueira P, Munoz-Guardiola P, Sole-Sanchez S, Megias-Roda E, Perez-Montoyo H, Jauregui P, Yeste-Velasco M, Gomez-Ferreria M, Erazo T, Ametller E, Recalde-Percaz L, Moragas-Garcia N, Noguera-Castells A, Mancino M, Moran T, Nadal E, Alfon J, Domenech C, Gascon P, Lizcano JM, Fuster G, Bragado P. The novel proautophagy anticancer drug ABTL0812 potentiates chemotherapy in adenocarcinoma and squamous nonsmall cell lung cancer. Int J Cancer. 2020 Aug 15;147(4):1163-1179. doi: 10.1002/ijc.32865. Epub 2020 Feb 6.

  PMID: 31943158 BACKGROUND

• Vidal L, Victoria I, Gaba L, Martin MG, Brunet M, Colom H, Cortal M, Gomez-Ferreria M, Yeste-Velasco M, Perez A, Rodon J, Sohal DPS, Lizcano JM, Domenech C, Alfon J, Gascon P. A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours. Eur J Cancer. 2021 Mar;146:87-94. doi: 10.1016/j.ejca.2020.12.019. Epub 2021 Feb 12.

  PMID: 33588149 BACKGROUND

• Paris-Coderch L, Soriano A, Jimenez C, Erazo T, Munoz-Guardiola P, Masanas M, Antonelli R, Boloix A, Alfon J, Perez-Montoyo H, Yeste-Velasco M, Domenech C, Roma J, Sanchez de Toledo J, Moreno L, Lizcano JM, Gallego S, Segura MF. The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis. Cell Death Dis. 2020 Sep 17;11(9):773. doi: 10.1038/s41419-020-02986-w.

  PMID: 32943619 BACKGROUND

• Mancini A, Colapietro A, Cristiano L, Rossetti A, Mattei V, Gravina GL, Perez-Montoyo H, Yeste-Velasco M, Alfon J, Domenech C, Festuccia C. Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models. Front Oncol. 2022 Nov 2;12:943064. doi: 10.3389/fonc.2022.943064. eCollection 2022.

  PMID: 36408162 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

ABTL0812; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Carles Domènech, PhD

  Ability Pharmaceuticals SL

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2018
• First Posted: January 31, 2018
• Study Start: April 26, 2021
• Primary Completion: April 26, 2023
• Study Completion: December 31, 2025
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)