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

NCT03429218 | Completed Phase 1 FDA Drug

• 1 other identifier: TP-0184-101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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 1, open-label, dose-escalation, safety, pharmacokinetics, and pharmacodynamic study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral TP-0184 administered once weekly for 4 weeks in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Keywords

Sumitomo Dainippon Pharma Oncology SDPO; Phase 1; First in human; Solid Tumors; Advanced Malignancy; Cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events

  A DLT is defined as any one of the following events observed within Cycle 1 regardless of investigator attribution unless there is a clear alternative explanation: * Grade 3 or greater febrile neutropenia * Grade 4 neutropenia for ≥7 consecutive days * Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with clinically significant bleeding or that requires a platelet transfusion * Grade 3 or 4 nonhematologic AEs including nausea, vomiting, diarrhea, and electrolyte imbalances persisting for more than 48 hours despite optimal medical management * Dosing delays ≥1 week due to treatment emergent adverse events or related severe laboratory test values

  Day 1 - 28

• Determine maximum tolerated dose (MTD)

  If a patient experiences a DLT, up to three additional patients will be treated at that dose level. If no additional DLTs are observed in the expanded six-patient cohort, the dose will be escalated in a new cohort of three patients. If two or more patients at a given dose level experience a DLT during the first cycle, then the MTD will have been exceeded and up to a total of six patients will be treated at the next lower dose level. If 0 or 1 of 6 patients experiences a DLT at this previous lower dose level, this dose will be declared the MTD.

  20 months

Secondary Outcomes (2)

• Recommended Phase 2 Dose of TP-0184

  23 months

• Determine antitumor activity of TP-0184

  20 months

Study Arms (1)

Single Arm TP-0184

EXPERIMENTAL

Weekly dose of TP-0184 by oral administration

Drug: TP-0184

Interventions

TP-0184 DRUG

Oral dose once weekly for 4 weeks

Single Arm TP-0184

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (5)

Honor Health

Scottsdale, Arizona, 85258, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital MGH

Boston, Massachusetts, 02215, United States

Location

University of Texas Southwestern UTSW

Dallas, Texas, 75390-9179, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Officials

• Greg Pennock, MD

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

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: February 5, 2018
• First Posted: February 12, 2018
• Study Start: July 10, 2018
• Primary Completion: March 8, 2021
• Study Completion: March 8, 2021
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)