Vactosertib With Nal-IRI/FL In Metastatic Pancreatic Ductal Adenocarcinoma.

Study Overview

Vactosertib With Nal-IRI/FL in Metastatic Pancreatic Ductal Adenocarcinoma.

To determine recommended phase 2 dose and to evaluate the safety of vactosertib in combination with nal-IRI/FL in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have failed first-line gemcitabine and nab-paclitaxel

* Number of patients : Total 24 patients (6-12 patients in phase 1 part and 12 patients in expansion cohort ) * Treatment : * Vactosertib* 100-300 mg bid for 5 days * Liposomal Irinotecan (Onivyde) 70mg/m2 on D1 * LV 200mg/m2 IV bolus on D1 * 5-FU 2400mg/m2 CIV over 46 hours on D1 * Vactosertib will be kindly provided by MedPacto. * Disease evaluation: Tumor assessment will be conducted at screening and before Day 1 of every third cycle starting with Cycle 4 * Period : Approximately 24 months from the date of Institutional Review Board (IRB) approval * Primary endpoint : To determine recommended phase 2 dose and to evaluate the safety of vactosertib in combination with nal-IRI/FL in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have failed first-line gemcitabine and nab-paclitaxel * Secondary endpoint : * Progression-Free Survival (PFS) (RECIST 1.1 criteria) * Overall Survival (OS) * Objective Response Rate (ORR) (RECIST 1.1 criteria) * Disease Control Rate (DCR) (RECIST 1.1 criteria) * Exploratory endpoint * Pharmacokinetic assessment: before treatment, post treatment 1.5h, 4.5h, and 8hPharmacodynamic assessment: to evaluate changes in the amount of p-SMAD in PBMC. * Biomarker analysis in pre-treated and post-treated tumor samples

Pancreas Cancer

DRUG: Vactosertib

2019-10-054

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-01-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-06-13
First Submitted that Met QC Criteria 2020-02-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-06-15
First Posted (ACTUAL) 2020-02-06	Results First Posted N/A	Last Verified 2022-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: open label,single arm Vactosertib* 100-300 mg bid for 5 days + Liposomal Irinotecan (Onivyde) 70mg/m2 + LV 200mg/m2 IV bolus + 5-FU 2400mg/m2 CIV over 46 hours	DRUG: Vactosertib Vactosertib: 50-mg white round film-coated tablets containing excipients (lactose monohydrate Fastflo 316, microcrystalline cellulose Avicel PH 102, crospovidone Kollidon CL-F, povidone Kollidon 30, magnesium stearate, opadry white) and active pharmaceuti

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: open label,single arm

Vactosertib* 100-300 mg bid for 5 days + Liposomal Irinotecan (Onivyde) 70mg/m2 + LV 200mg/m2 IV bolus + 5-FU 2400mg/m2 CIV over 46 hours

DRUG: Vactosertib

Vactosertib: 50-mg white round film-coated tablets containing excipients (lactose monohydrate Fastflo 316, microcrystalline cellulose Avicel PH 102, crospovidone Kollidon CL-F, povidone Kollidon 30, magnesium stearate, opadry white) and active pharmaceuti

Primary Outcome Measures	Measure Description	Time Frame
Progression-Free Survival (PFS)		up to 6 weeks

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
19 Years

Accepts Healthy Volunteers:

bilirubin ≤ 1.5 x ULN (upper limit of normal)
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault)
partial thromboplastin time (aPTT) ≤ 1.5 x ULN
absolute neutrophil count (ANC) ≥ 1,500 cells/µL
platelet count ≥ 100,000/µL
hemoglobin ≥ 9.0 g/dL 5. Subjects who have at least a 12-week life expectancy at the Investigator's discretion 6. Subjects who have Eastern Cooperative Oncology Group (ECOG)Performance Status 0-1

Subjects who have myocardial infarction, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension within 6 months before screening
Subjects who have major abnormalities at the Investigator's discretion based on electrocardiogram (ECG)and Doppler ECHO results at screening or within 14 days before screening
Subjects who have increase in brain natriuretic peptide (BNP) or increase in troponin (over 99th percentile upper reference limit) at Screening (based on the normal range of relevant study center)
Subjects who have risk factors for ascending aortic aneurysm such as genetic disorder and trauma and risk factors for aortic stenosis
Subjects who have a history of heart or aorta surgery 5. Subjects who have clinically significant gastrointestinal bleeding within 4 weeks before screening 6. Subjects who have a known history or suspected hypersensitivity to any excipients of the investigational product or combination drug(s) 7. Subjects who have received prior treatment targeting the signaling pathway of TGF-β 8. Subjects who have a disease or condition that affects the mechanism of the investigational product, or are currently using or planning to use:

Drugs that are exclusively or primarily eliminated by cytochrome P-450 isozyme (CYP) including CYP1A2, CYP2B6, or CYP3A4
Drugs that are exclusively or primarily eliminated by UDP glucuronyltransferase (UGT) 1A1 (UGT1A1)
Drugs that are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window or are strong inhibitors of drug transporter MDR1
Drugs that are strong inhibitors or inducers of CYP2D6 or CYP3A4 9. Subjects who are unable to swallow tablets 10. Subjects who have a history of or are suspected of drug abuse 11. Female subjects of child-bearing potential who have a positive result on a pregnancy test at screening or are unable to agree to use an effective barrier method of birth control to avoid pregnancy during the study period (e.g., sterilization, intrauterine contraceptive device, combination of oral contraception and barrier contraception, combination of other hormone delivery systems and barrier contraception, contraceptive cream, combination of cream, jelly, or form and diaphragm or condom) 12. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study 13. Subjects who were treated with other investigational products within 28 days before screening or within a period shorter than 5-timesthe half-life of the investigational product

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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