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ABTL0812 in Combination With FOLFIRINOX for First-line Treatment of Metastatic Pancreatic Study (PanC-ASAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04431258
Recruitment Status : Recruiting
First Posted : June 16, 2020
Last Update Posted : November 14, 2022
Sponsor:
Information provided by (Responsible Party):
Ability Pharmaceuticals SL

Brief 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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: ABTL0812 Drug: Folfirinox Drug: Placebo Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double blind, randomized, placebo-controlled, multicenter study
Masking: Single (Care Provider)
Primary Purpose: Treatment
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
Actual Study Start Date : May 6, 2021
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : March 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A) ABTL0812 + FOLFIRINOX

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 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.

Drug: ABTL0812
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.

Drug: Folfirinox

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.
Other Name: Chemotherapy

Experimental: Arm B) PLACEBO + FOLFIRINOX

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 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.

Drug: ABTL0812
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.

Drug: Placebo
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.




Primary Outcome Measures :
  1. Phase I - RP2D [ Time Frame: 5 weeks ]
    Recommended Phase II Dose (RP2D) of ABTL0812 in combination with FOLFIRINOX

  2. Phase II - PFS [ Time Frame: 1 year ]
    PFS using RECIST v1.1 by central review


Secondary Outcome Measures :
  1. PFS [ Time Frame: 1 year ]
    PFS using RECIST v1.1 by investigator analysis

  2. ORR [ Time Frame: 1 year ]
    Objective response rate

  3. PFS 6 m [ Time Frame: 6 months ]
    PFS

  4. TTR [ Time Frame: 1 year ]
    Time to response

  5. DOR [ Time Frame: 1 year ]
    Duration of response

  6. OS [ Time Frame: 5 years ]
    Overall survival

  7. OS 1y [ Time Frame: 1 year ]
    Overall survival

  8. Adverse events [ Time Frame: 1 year ]
    Number of participants with Adverse Events (AE). AEs classified according to CTCAE v5.0


Other Outcome Measures:
  1. PK - Cmax [ Time Frame: 1 month ]
    Determination of peak plasma concentration

  2. PK - AUC [ Time Frame: 1 month ]
    Determinatoin of Area under the plasma concentration versus time curve

  3. Quality of Life Questionnaire QLC-C30 [ Time Frame: 1 year ]
    Quality of life measured with questionnaires QLC-C30

  4. Quality of Life Questionnaire QLQ-PAN26 [ Time Frame: 1 year ]
    Quality of life measured with questionnaires QLQ-PAN26



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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. Adequate hematologic function, measured as:

    • absolute neutrophil count ≥ 1.5x109/L
    • platelet count ≥ 100x109/L without transfusion support
    • hemoglobin ≥ 10 g/dL
  7. Total bilirubin ≤ 1.5 x ULN
  8. Albumin ≥ 3.3 g/dL
  9. AST (SGOT) and ALT (SGPT) ≤ 2.5 times x upper limit of normal (≤ 5 times the ULN in patients with evidence of liver metastases)
  10. Alkaline phosphatase ≤ 2.5 times ULN (≤5 times the ULN in patients with evidence of liver metastases)
  11. Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
  12. 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.
  13. 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.
  14. Willing and able to provide informed consent
  15. Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol.

Exclusion criteria

  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. Patients unable to provide informed consent like those under administrative or legal supervision

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04431258


Contacts
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Contact: Marc Cortal +34603141706 contact@abilitypharma.com

Locations
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United States, Kansas
University of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205-0000
Contact: Anup Kasi, MD         
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Colin Weekes, MD, PhD         
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Davendra Sohal         
France
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Antoine Hollebecque         
Spain
ICO Badalona Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Laura Layos-Romero         
Centro Oncológico de Galicia Recruiting
A Coruña, Galicia, Spain, 15009
Contact: Manuel Ramos Vázquez         
Hospital General Universitario Dr. Balmis Recruiting
Alicante, Spain, 03010
Contact: Bartomeu Massutí Sureda         
Vall d'Hebron University Hospital Recruiting
Barcelona, Spain, 08035
Contact: Teresa Macarulla         
ICO Girona Recruiting
Girona, Spain, 17007
Contact: Adelaida García         
Hospital Universitari Arnau de Vilanova Recruiting
Lleida, Spain, 25198
Contact: Alberto Rodrigo-Cáceres         
Hospital General Universitario Morales Meseguer Recruiting
Murcia, Spain, 30008
Contact: Alberto Carmona         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Inmaculada Gallego-Gimenez         
Hospital Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Susana Rosello         
Hospital Universitario Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Roberto Pazo Cid         
Sponsors and Collaborators
Ability Pharmaceuticals SL
Investigators
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Study Director: Marc Cortal Ability Pharmaceuticals SL
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ability Pharmaceuticals SL
ClinicalTrials.gov Identifier: NCT04431258    
Other Study ID Numbers: ABT-C11-2020
2020-002791-13 ( EudraCT Number )
FD-R-006817-01 ( Other Grant/Funding Number: FDA OOPD )
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Folfirinox
Antineoplastic Agents