A Study to Assess the Efficacy and Safety of ABTL0812

NCT03366480 | Completed Phase 1 DMC

• 2 other identifiers: ABT-C5-20162016-001352-21
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

A phase I/ II, open label study to assess the efficacy and safety of ABTL0812 in combination with paclitaxel and carboplatin in patients with advanced endometrial cancer or squamous NSCLC.

Conditions

Endometrial Cancer; Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Emergent Adverse Events

  Related Adverse Events as Assessed by CTCAE v4.03

  1 year

Secondary Outcomes (4)

• Objective response rate (ORR)

  2 years

• Progression Free Survival (PFS)

  2 years

• Time to Progression (TP)

  2 years

• Duration of Response (DR)

  2 years

Study Arms (2)

Endometrial cancer

EXPERIMENTAL

ABTL0812 (starting 1,300 mg tid orally) in combination with paclitaxel and carboplatin will be given to patients with advanced endometrial cancer, up to 12 months from initiation.

Drug: ABTL0812 in combination with paclitaxel and carboplatin

Squamous non-small cell lung cancer

EXPERIMENTAL

ABTL0812 (starting 1,300 mg tid orally) in combination with paclitaxel and carboplatin will be given to patients with squamous NSCLC, up to 12 months from initiation.

Drug: ABTL0812 in combination with paclitaxel and carboplatin

Interventions

ABTL0812 in combination with paclitaxel and carboplatin DRUG

ABTL0812 in combination with paclitaxel and carboplatin.

Endometrial cancer; Squamous non-small cell lung cancer

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
• For endometrial cancer: Patients with advanced, metastatic or recurrent endometrial cancer, from all histological types except carcinosarcoma and leiomyosarcoma.
• For squamous NSCLC: Patients with histologically or radiological/cytologically confirmed diagnosis (non-irradiance IIIb stage or stage IV), excluding mixed tumors, neuroendocrine or adenocarcinoma.
• Have adequate tumor tissue available (either archival not older than 6 months or new tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample should be provided, if available.
• Life expectancy ≥ 12 weeks in the opinion of the investigator
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Contraception: All female patients will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months' consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically. Female patients of childbearing potential must agree to use two forms of highly effective contraception methods during the study and for a period of 6 months following the last administration of the study drug. Male patients and their female partners, who are of childbearing potential and are not practicing total abstinence, must agree to use two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug.
• Adequate bone marrow function defined as:
• absolute neutrophil count ≥ 1.5x109/L
• platelet count ≥ 100x109/L
• hemoglobin ≥ 10.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal
• Aspartate transaminase (AST) ≤ 2.5 times upper limit of normal (ULN) (≤5 times the ULN in patients with evidence of liver metastases)

You may not qualify if:

• Patients previously treated with an inhibitor of the Phosphoinositide 3-kinase/Protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway.
• Patients with symptomatic brain metastases. Patients with asymptomatic and treated brain metastases can be included in the study if they are kept on stable doses of steroids for a period of 1 month prior to study entry provided they don't have peripheric neuropathy grade 2 or superior.
• Patients with gastrointestinal abnormalities including inability to take oral medications, malabsorption syndromes or other clinically significant gastrointestinal abnormalities that may impair the absorption of the investigational medicinal product.
• Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start.
• Patients with myocardial infarction within ≤ 12 months prior to study entry, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication.
• Evidence of pre-existing uncontrolled hypertension. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
• Patients with active Hepatitis B or C or human immunodeficiency virus (HIV) infection with non-controlled disease according to the treating physician.
• Patients with any other medical conditions (such as psychiatric illness, 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.

Sponsors & Collaborators

• Ability Pharmaceuticals SL: lead
• Hospital Vall d'Hebron: collaborator
• Institut Català d'Oncologia: collaborator
• Hospital Clínico Universitario de Valencia: collaborator
• Hospitales Universitarios Virgen del Rocío: collaborator
• Centre Leon Berard: collaborator
• Institut Paoli-Calmettes: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator

Study Sites (1)

Abilitypharma

Barcelona, 08290, Spain

Location

Related Publications (9)

• 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

• Leary A, Estevez-Garcia P, Sabatier R, Ray-Coquard I, Romeo M, Barretina-Ginesta P, Gil-Martin M, Garralda E, Bosch-Barrera J, Moran T, Martin-Martorell P, Nadal E, Gascon P, Rodon J, Lizcano JM, Munoz-Guardiola P, Fierro-Duran G, Pedros-Gamez O, Perez-Montoyo H, Yeste-Velasco M, Cortal M, Perez-Campos A, Alfon J, Domenech C, Perez-Fidalgo A, Oaknin A. ENDOLUNG trial. A phase 1/2 study of the Akt/mTOR inhibitor and autophagy inducer Ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with advanced/recurrent endometrial cancer. BMC Cancer. 2024 Jul 22;24(1):876. doi: 10.1186/s12885-024-12501-5.

  PMID: 39039449 DERIVED

• Polonio-Alcala E, Sole-Sanchez S, Munoz-Guardiola P, Megias-Roda E, Perez-Montoyo H, Yeste-Velasco M, Alfon J, Lizcano JM, Domenech C, Ruiz-Martinez S, Puig T. ABTL0812 enhances antitumor effect of paclitaxel and reverts chemoresistance in triple-negative breast cancer models. Cancer Commun (Lond). 2022 Jun;42(6):567-571. doi: 10.1002/cac2.12282. Epub 2022 Mar 16. No abstract available.

  PMID: 35293148 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

ABTL0812; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Ana Oaknin

  VHIO

  PRINCIPAL INVESTIGATOR

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: November 15, 2017
• First Posted: December 8, 2017
• Study Start: December 1, 2016
• Primary Completion: June 1, 2020
• Study Completion: November 15, 2020
• Last Updated: February 22, 2023

Record last verified: 2023-02

Locations

ES (1)