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
- Conditions
- Metastatic pancreatic cancerMedDRA version: 21.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002791-13-FR
- Lead Sponsor
- Ability Pharmaceuticals, S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 144
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 (requested only for 50% of patients in each treatment arm): have adequate tumor tissue or cytology available (either archival or new tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample should be provided, if available.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 144
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144
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
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. 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.
10. Patient has active Hepatitis B or C, human immunodeficiency virus (HIV) or Covid-19 infection with non-controlled disease according to the treating physician.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Phase I:<br>• Safety of ABTL0812 plus FOLFIRINOX<br><br>Phase II:<br>• To determine the efficacy of ABTL0812 in combination with FOLFIRINOX vs. FOLFIRINOX plus placebo by progression free survival (PFS) according to central review;Secondary Objective: Phase I:<br>• To determine the efficacy of ABTL0812 in combination with FOLFIRINOX<br>• Pharmacokinetics of ABTL0812<br>• Pharmacodynamic biomarkers<br><br>Phase II:<br>• To determine the efficacy of ABTL0812 in combination with<br>FOLFIRINOX vs. FOLFIRINOX plus placebo<br>• To determine the safety and tolerability of ABTL0812 plus<br>FOLFIRINOX<br>• Pharmacokinetics of ABTL0812<br>• Pharmacodynamic biomarkers<br>;Primary end point(s): Phase I: Recommended Phase II Dose (RP2D) of ABTL0812 in<br>combination with FOLFIRINOX<br><br>Phase II: PFS using RECIST v1.1 by central review;Timepoint(s) of evaluation of this end point: Phase I: After 2nd chemotherapy cycle (4 weeks)<br>Phase II: 1 year
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Phase I:<br>• PFS using RECIST v1.1 by investigator analysis<br>• Objective response rate (ORR)<br>• PFS at 6 months<br>• Pharmacokinetic analysis of plasma samples<br>• Analysis of TRIB3 and CHOP in blood samples. Additional biomarkers<br>might be included.<br><br>Phase II:<br>• PFS using RECIST v1.1 by investigator analysis<br>• Objective response rate (ORR)<br>• PFS at 6 months<br>• Time to response (TTR)<br>• Duration of response (DOR)<br>• Overall survival (OS)<br>• OS at 1 year<br>• Adverse Events (AE) physical examination, vital signs and laboratory<br>findings according to Common Terminology Criteria for Adverse Events<br>(CTCAE) v5.0<br>• Pharmacokinetic analysis of plasma samples<br>• Analysis of TRIB3 and CHOP in blood samples. Additional biomarkers<br>might be included.;Timepoint(s) of evaluation of this end point: Phase I and II: 1 year