First in Human Dose Escalation Study of Vactosertib (TEW-7197) in Subjects With Advanced Stage Solid Tumors

NCT02160106 | Completed Phase 1

• 1 other identifier: MP-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief Summary

The phase I dose escalation study will investigate the safety, tolerability, and pharmacokinetics of the TGF-β pathway inhibitor TEW 7197 in subjects with advanced, refractory solid tumors.

Conditions

Advanced Stage Solid Tumors

Keywords

Cancer; advanced solid tumors; metastatic; phase I; transforming growth factor beta; TGF-β; first-in-human; TEW-7197; activin receptor-like kinase 5; ALK5; Smad2; Smad3; phospho-Smad; phospho Smad; psmad; serine / threonine kinase inhibitor; pharmacokinetics; MedPacto; National OncoVenture

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) based on the number of subjects experiencing at least 1 DLT

  28 days

Secondary Outcomes (1)

• Dose-dependency of toxicity based on: dose limiting toxicities; frequency, type, grade, and seriousness, and causality of treatment-emergent adverse events, and laboratory assessments.

  while undergoing study treatment and up to 30 days after the last dose of TEW-7197

Study Arms (1)

TEW-7197

EXPERIMENTAL

Dose Escalation of TEW-7197: TEW 7191 tablets will be given once daily (QD) or twice daily (BID) for 5 days followed by 2 days without treatment in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons.

Drug: TEW-7197

Interventions

TEW-7197 DRUG

Single daily doses by oral administration on Days 1, 2, 3, 4, 5, Days 8, 9, 10, 11, 12, Days 15, 16, 17, 18, 19 and Days 22, 23, 24, 25, 26 of each 28 day cycle. Starting dose is 30 mg, with escalation to 60 mg, and subsequent dose escalation using a modified Fibonacci algorithm.

Also known as: EW-7197, EW7197

TEW-7197

Eligibility Criteria

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

You may qualify if:

• Advanced stage solid tumors as documented by histological or cytological evidence, with no available approved therapies known to cure metastatic disease or extend survival, and who have received all standard therapy.
• Documented disease progression following prior therapy, as assessed by the Investigator.
• Eastern Cooperative Oncology Group (ECOG) 0 or 1.
• Evaluable or measurable disease as defined by RECIST v1.1 may be enrolled in the dose escalation part; for the dose confirmation part, subjects must have measurable disease by RECIST v1.1 or biomarker for response.
• Males and females ≥ 18 years of age.
• Able to give written informed consent.
• Able to swallow tablets.
• Willing and able to comply with scheduled visits, treatment plans, laboratory tests and procedures.
• Acceptable liver function:
• Bilirubin ≤ 1.5 times the upper limit of normal (ULN),
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN; if liver metastases are present, then ≤ 5 times the ULN is allowed.
• Acceptable renal function:
• \*Serum creatinine ≤ 1.5 times the ULN.
• Acceptable hematologic status (without growth factor support or transfusion dependency):
• Absolute neutrophil count (ANC) ≥ 1,500 cells/μL,

You may not qualify if:

• Elevated Troponin 1 levels at screening or known to have persistently elevated brain natriuretic peptide (BNP).
• Serious pre-existing medical conditions as follows:
• Myocardial infarction within 6 months prior to screening, or pericardial effusion,
• History of cardiac or aortic surgery,
• Serious arrhythmia,
• Unstable angina pectoris,
• Congestive heart failure of New York Heart Association class III/IV,
• Hypertension that is not controlled by standard medication (to 150/90 mmHg or below),
• Cirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,
• Severe diabetes that is not currently controlled,
• Current or history of interstitial pneumonitis,
• Presence of aneurisms of the ascending aorta or aortic stress.
• Uncontrolled metastatic disease to the brain or central nervous system (CNS).
• Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
• Received prior treatment targeting the signaling pathway of TGF-β.

Sponsors & Collaborators

• MedPacto, Inc.: lead
• National OncoVenture: collaborator

Study Sites (3)

Unknown Facility

Durham, North Carolina, 27710, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Camurati-Engelmann Syndrome; Keratoacanthoma familial

Interventions

vactosertib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ilho Ha, PhD

  MedPacto, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 10, 2014
• Study Start: July 29, 2014
• Primary Completion: July 31, 2018
• Study Completion: August 28, 2018
• Last Updated: May 9, 2019

Record last verified: 2019-05

Locations

US (3)