Multi-center, Open-label, Phase 1b Clinical Trial to Evaluate the Safety, Tolerability, and Exploratory Efficacy of TEW-7197 in Combination With FOLFOX in Patients With Metastatic Pancreatic Ductal Adenocarcinoma Who Have Failed First-Line Gemcitabine and Nab-Paclitaxel

NCT03666832 | Unknown Phase 1

• 1 other identifier: 2017-10-150
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

• bilirubin ≤ 1.5 x ULN (upper limit of normal)
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
• serum creatinine ≤ 1.5 x ULNor 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
• Subjects who have at least a 12-week life expectancy at the Investigator's discretion
• Subjects who have Eastern Cooperative Oncology Group (ECOG)Performance Status 0-1
• Exclusion
• Subjects who were treated with surgery, radiotherapy, chemotherapy or investigational therapy within 2 weeks (note: placement of biliary stent is allowed)
• Subjects who have uncontrolled CNS metastases (patients who require steroids should be on a stable or decreasing dose for at least 2 weeks)
• Subjects who have any contraindications for 5-FU, leucovorin, or oxaliplatin
• Subjects who have moderate or severe cardiovascular disease
• 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
• Subjects who have clinically significant gastrointestinal bleeding within 4 weeks before screening
• Subjects who have a known history or suspected hypersensitivity to any excipients of the investigational product or combination drug(s)
• Subjects who have received prior treatment targeting the signaling pathway of TGF-β
• 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
• Subjects who are unable to swallow tablets
• Subjects who have a history of or are suspected of drug abuse
• 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)
• Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study
• 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

Conditions

Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• pregression free survival

  up to 6 weeks

Study Arms (1)

Arm1

EXPERIMENTAL

TEW-7197 100mg will be administered orally once a day 5days and rest 2days. Study treatment will be continued until objective disease progression.

Drug: TEW-7197

Interventions

TEW-7197 DRUG

TEW-7197 1cycle 14days -intake 5days, rest 2days

Also known as: TEW-7197, FOLFOX

Arm1

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Subjects who are males or females ≥ 19 years of age 2) Subjects who have the following history of first-line gemcitabine and nab-paclitaxel among patients with cytologically or histologically proven metastatic pancreatic ductal adenocarcinoma 3) Subjects who can give written informed consent for participation in this trial after receiving explanations of this trial 4) Subjects who have the following laboratory test values:
• bilirubin ≤ 1.5 x ULN (upper limit of normal)
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
• serum creatinine ≤ 1.5 x ULNor 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

You may not qualify if:

• \) Subjects who were treated with surgery, radiotherapy, chemotherapy or investigational therapy within 2 weeks (note: placement of biliary stent is allowed) 2) Subjects who have uncontrolled CNS metastases (patients who require steroids should be on a stable or decreasing dose for at least 2 weeks) 3) Subjects who have any contraindications for 5-FU, leucovorin, or oxaliplatin 4) Subjects who have moderate or severe cardiovascular disease
• 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

Sponsors & Collaborators

• Joon Oh Park: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Folfox protocol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

joonoh park, Ph MD

CONTACT

82-2-2148-7394; oncopark66@skku.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Samsung Medical Center

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 12, 2018
• Study Start: June 17, 2019
• Primary Completion: December 1, 2022
• Study Completion: December 30, 2023
• Last Updated: June 15, 2022

Record last verified: 2022-06

Locations

KR (1)