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Pancreatic CancerPhase 1/2PanC-ASAPNCT04431258

ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study

A Phase 1/2 study testing ABTL0812 and Folfirinox in people with Pancreatic Cancer, run by Ability Pharmaceuticals SL at 24 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Funded by: FDA OOPD (Grant #FD-R-006817-01), H2020 EIC Accelerator (Grant #954825) and Ability Pharmaceuticals SL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Cancer
What is being tested?
ABTL0812 and Folfirinox
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
24 sitesin 4 countries
Study dates
6 May 2021to 10 Jan 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed carcinoma, adenocarcinoma or ductal adenocarcinoma of the pancreas.
  • Confirmed metastatic disease
  • 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.
  • Age, older than 18 years old
  • Adequate hematologic function, measured as:
Show all 18Show fewer
  • absolute neutrophil count ≥ 1.5x109/L
  • platelet count ≥ 100x109/L without transfusion support
  • hemoglobin ≥ 10 g/dL
  • Total bilirubin ≤ 1.5 x ULN
  • Albumin ≥ 3.3 g/dL
  • AST (SGOT) 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)
  • Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
  • 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.
  • 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.
  • Willing and able to provide informed consent
  • Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol.

Who cannot join

  • Patients with any histology other than carcinoma, adenocarcinoma or ductal adenocarcinoma (such as squamous cell, acinar cell, medullary, colloid, neuroendocrine, etc)
  • Patients has only locally advanced disease, resectable or borderline resectable.
  • The patient has received chemotherapy as adjuvant therapy for locally advanced disease, resectable or borderline resectable.
  • Patient has received previous abdominal radiotherapy, (with the exception of analgesic radiotherapy that was not performed on target lesions).
  • Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway by a systemic route.
  • History of chronic diarrhea or inflammatory disease of the colon or rectum, or occlusion or sub-occlusion not resolved under symptomatic treatment
Show all 12Show fewer
  • Patient is pregnant or in lactation period. High sensitivity pregnancy test (urine or serum) to be performed within 7 days before study treatment starts.
  • 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.
  • 12-lead ECG with clinically relevant abnormality or showing a QTcF >450 ms, PR >210 ms, or QRS >120 ms at screening.
  • 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.
  • Patient has active Hepatitis B or C, human immunodeficiency virus (HIV) or Covid-19 infection with non-controlled disease according to the treating physician.
  • Patients unable to provide informed consent like those under administrative or legal supervision

Trial locations and contacts

24 sites in 4 countries.

24 sites in 4 countries

Spain14 sites

  • Centro Oncológico de Galicia

    A Coruña, Galicia, 15009

  • Hospital General Universitario Dr. Balmis

    Alicante, 03010

  • ICO Badalona

    Badalona, Barcelona, 08916

  • Hospital Quiron Salud

    Barcelona, 08023

  • Vall d'Hebron University Hospital

    Barcelona, 08035

  • ICO Girona

    Girona, 17007

  • Hospital Universitari Arnau de Vilanova

    Lleida, 25198

  • Hospital Gregorio Marañón

    Madrid, 28009

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital General Universitario Morales Meseguer

    Murcia, 30008

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Universitario de Toledo

    Toledo, 45007

  • Hospital Universitario de Valencia

    Valencia, 46010

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

United States4 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Cedars Sinai

    Los Angeles, California, 90048

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205-0000

Other trials in United States

France3 sites

  • CGFL Dijon

    Dijon, 21000

  • Institute Paoli-Calmettes

    Marseille, 13009

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Israel3 sites

  • Rabam MC

    Haifa

  • Shaare Zedek MC

    Jerusalem

  • Sheba MC

    Ramat Gan

Other trials in Israel

About this study

Official title: 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

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. Funded by: FDA OOPD (Grant #FD-R-006817-01), H2020 EIC Accelerator (Grant #954825) and Ability Pharmaceuticals SL.

Read the detailed description

Phase I: This is an open label Phase I to determine the RP2D of ABTL0812 in combination with FOLFIRINOX. All patients will receive ABTL0812 in combination with FOLFIRINOX.

A dose de-escalation phase will be performed in which up to 3 different ABTL0812 dose levels will be tested in combination with FOLFIRINOX. ABTL0812 doses are: 1300 mg tid (starting dose), followed (if necessary) by 975 mg tid and 650 mg tid. Patient intra-escalation is not allowed.

Phase II: This is a double blind, randomized, placebo-controlled Phase II multicenter study to evaluate ABTL0812 in combination with FOLFIRINOX for first-line treatment of metastatic pancreatic cancer. Patients will be randomized to one of two groups: arm A) receiving ABTL0812 in addition to FOLFIRINOX and arm B) receiving FOLFIRINOX plus placebo.

Arm A) ABTL0812 + FOLFIRINOX Arm B) PLACEBO + FOLFIRINOX

Being tested
ABTL0812, Folfirinox, Placebo
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABTL0812Drug

    ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.

  • FolfirinoxDrug

    Also called Chemotherapy

    FOLFIRINOX will be dosed according to the standard following regimen:

    • oxaliplatin 85 mg/m2, administered as 2-hour iv infusion
    • leucovorin 400 mg/m2, administered as 2-hour iv infusion
    • irinotecan 180 mg/m2, administered as 1.5-hour iv infusion
    • fluorouracil 2400 mg/m2, administered as 46-hour iv infusionevery 2 weeks (=1 cycle) until disease progression or unacceptable toxicities.

  • PlaceboDrug

    Placebo will be administered daily at the same regim as ABTL0812. Placebo will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued, if the patient is in response or stable disease.

Study groups in NCT04431258
Study groupRoleWhat they receive
Arm A) ABTL0812 + FOLFIRINOXExperimentalFOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. ABTL0812 will be administered daily at its RP2D. ABTL0812 will be administered as single agent during a run-in period of one week before starting the first cycle of FOLFIRINOX, then daily during chemotherapy cycles. Also, ABTL0812 will be maintained once chemotherapy is discontinued, if ABTL0812 is tolerated and if the patient is in response or stable disease.
Receives: Drug: ABTL0812; Drug: Folfirinox
Arm B) PLACEBO + FOLFIRINOXExperimentalFOLFIRINOX will be dosed according to the standard following regimen: * oxaliplatin 85 mg/m2, administered as 2-hour iv infusion * leucovorin 400 mg/m2, administered as 2-hour iv infusion * irinotecan 180 mg/m2, administered as 1.5-hour iv infusion * fluorouracil 2400 mg/m2, administered as 46-hour iv infusion every 2 weeks (=1 cycle) until disease progression or unacceptable toxicities. Placebo will be administered at the same volume than ABTL0812 in arm A) FOLFIRINOX, then daily during chemotherapy cycles. Also, placebo will be maintained once chemotherapy is discontinued.
Receives: Drug: ABTL0812; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I - RP2D

    Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX

    Measured: 5 weeks

  2. Phase II - PFS

    PFS using RECIST v1.1 by central review

    Measured: 1 year

Secondary outcomes (8)

  1. PFS

    PFS using RECIST v1.1 by investigator analysis

    Measured: 1 year

  2. ORR

    Objective response rate

    Measured: 1 year

  3. PFS 6 m

    PFS

    Measured: 6 months

  4. TTR

    Time to response

    Measured: 1 year

  5. DOR

    Duration of response

    Measured: 1 year

  6. OS

    Overall survival

    Measured: 5 years

  7. OS 1y

    Overall survival

    Measured: 1 year

  8. Adverse events

    Number of participants with Adverse Events (AE). AEs classified according to CTCAE v5.0

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2020
  2. Study start6 May 2021
  3. Primary completion10 Jan 2024
  4. Study completion10 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double blind, randomized, placebo-controlled, multicenter study
Masking
Single blind
Who is masked
Care provider
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04431258
Sponsor's protocol ID
ABT-C11-2020
Other IDs
2020-002791-13, FD-R-006817-01
Acronym
PanC-ASAP
Status last verified
Mar 2024
First submitted
27 May 2020
Last updated
18 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26671995

  • 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.

    PubMed 32397857

  • 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.

    PubMed 30853360

  • 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.

    PubMed 31943158

  • 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.

    PubMed 33588149

  • 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.

    PubMed 32943619

  • 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.

    PubMed 36408162

  • 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.

    PubMed 35293148

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ABTL0812 and Folfirinox in people with Pancreatic Cancer, run by Ability Pharmaceuticals SL at 24 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Spain, United States, France, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - RP2D (time frame: 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04431258, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2024.

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