Status:

COMPLETED

First-in-human Study of Oral TP-0184 in Patients With Advanced Solid Tumors

Lead Sponsor:

Sumitomo Pharma America, Inc.

Conditions:

Advanced Solid Tumors

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

TP-0184 is a potent inhibitor of ALK2 or ACRV1 kinase, a constitutively active serine/threonine receptor kinase due to activating mutations or upregulated upstream signaling pathways. This is a Phase ...

Detailed Description

Primary Objective: • To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks, over a range of doses in patients with adv...

Eligibility Criteria

Inclusion

  • Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor
  • Be refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition.
  • Have one or more tumors measurable or evaluable as outlined by modified RECIST v1.1
  • Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization \[WHO\]) performance of ≤1
  • Have a life expectancy ≥3 months
  • Be ≥18 years of age
  • Have a negative pregnancy test (if female of childbearing potential)
  • Have acceptable liver function:
  • Bilirubin ≤1.5x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x upper limit of normal (ULN) \*If liver metastases are present, then ≤5x ULN is allowed.
  • Have acceptable renal function: Calculated creatinine clearance ≥ 30 mL/min
  • Have acceptable hematologic status:
  • Granulocyte ≥1500 cells/mm3
  • Platelet count ≥100,000 (plt/mm3)
  • Hemoglobin ≥8 g/dL (Patients may not have received prior transfusions within 2 weeks of the first dose of TP-0184)
  • Have acceptable coagulation status:
  • Prothrombin time (PT) within 1.5x normal limits
  • Activated partial thromboplastin time (aPTT) within 1.5x normal limits
  • Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation and for at least 3 months (males) and 6 months (females) after the last study drug dose. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Have read and signed the Institutional Review Board (IRB)-approved informed consent form (ICF) prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new ICF must be signed.)

Exclusion

  • History of congestive heart failure (CHF); cardiac disease, myocardial infarction within the past 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) \<45% by echocardiogram (ECHO), unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1
  • Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \>450 msec in men and \>470 msec in women
  • Have a seizure disorder requiring anticonvulsant therapy
  • Presence of symptomatic central nervous system metastatic disease or disease that requires local therapy such as radiotherapy, surgery, or increasing dose of steroids within the prior 2 weeks
  • Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
  • Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1
  • Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Are pregnant or nursing
  • Received treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within 28 days or 5 half lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
  • Are unwilling or unable to comply with procedures required in this protocol
  • Have known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible.
  • Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
  • Are currently receiving any other investigational agent
  • Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation
  • Have undergone significant surgery to the gastrointestinal tract that could impair absorption or that could result in short bowel syndrome with diarrhea due to malabsorption
  • Have hemochromatosis or a transferrin saturation (TS) \>50% in men or \>45% in women at baseline or noted during the study via scheduled iron panel monitoring

Key Trial Info

Start Date :

July 10 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

March 8 2021

Estimated Enrollment :

24 Patients enrolled

Trial Details

Trial ID

NCT03429218

Start Date

July 10 2018

End Date

March 8 2021

Last Update

November 14 2023

Active Locations (5)

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Page 1 of 2 (5 locations)

1

Honor Health

Scottsdale, Arizona, United States, 85258

2

Northside Hospital

Atlanta, Georgia, United States, 30342

3

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States, 66160

4

Massachusetts General Hospital MGH

Boston, Massachusetts, United States, 02215