Clinical Trials /

Study of TP-3654 in Patients With Advanced Solid Tumors

NCT03715504

Description:

TP-3654 is an oral PIM inhibitor. 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-3654 in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of TP-3654 in Patients With Advanced Solid Tumors
  • Official Title: A Phase I, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-3654 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TP-3654-101
  • NCT ID: NCT03715504

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
TP-3654Single Arm TP-3654

Purpose

TP-3654 is an oral PIM inhibitor. 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-3654 in patients with advanced solid tumors.

Detailed Description

      Primary Objective:

      • To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral
      TP-3654 in patients with advanced solid tumors.

      Secondary Objectives:

        -  To establish the pharmacokinetic (PK) profile of orally administered TP-3654

        -  To observe patients for any evidence of antitumor activity of TP-3654 by objective
           radiographic assessment

        -  To study the pharmacodynamic effects of TP-3654 therapy

        -  To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-3654
    

Trial Arms

NameTypeDescriptionInterventions
Single Arm TP-3654ExperimentalTP-3654 by oral administration
  • TP-3654

Eligibility Criteria

        Inclusion Criteria:

          -  1. Have a histologically confirmed diagnosis of advanced metastatic, progressive or
             unresectable solid tumor

             2. Be refractory to, or intolerant of, established therapy known to provide clinical
             benefit for their condition.

             3. Have 1 or more tumors measurable or evaluable as outlined by modified Response
             Evaluation Criteria in Solid Tumors (RECIST) v1.1

             4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than
             or equal to 2

             5. Have a life expectancy greater than or equal to 3 months

             6. Be greater than or equal to 18 years of age

             7. Have a negative pregnancy test (if female of childbearing potential) and not
             currently nursing

             8. Have acceptable liver function:

             a. Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless associated
             with Gilbert's syndrome b. Aspartate aminotransferase (AST/SGOT), alanine
             aminotransferase (ALT/SGPT) and alkaline phosphatase less than or equal to 2.5x upper
             limit of normal (ULN) *If liver metastases are present, then less than or equal to 5x
             ULN is allowed.

             9. Have acceptable renal function:

             a. Calculated creatinine clearance greater than or equal to 30 mL/min

             10. Have acceptable hematologic status:

             a. Granulocyte greater than or equal to 1500 cells/mm3 b. Platelet count greater than
             or equal to 100,000 (plt/mm3) c. Hemoglobin greater than or equal to 8 g/dl

             11. Have acceptable coagulation status:

               1. Prothrombin time (PT) within 1.5x normal limits

               2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits

                  12. 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 6 months 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.

                  13. Have read and signed the Institutional Review Board (IRB)-approved informed
                  consent form 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 informed consent form must be signed.)

                  Exclusion Criteria:

          -  1. 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
             <45% by echocardiogram, unstable arrhythmia, or evidence of ischemia on
             electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1

             2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450
             msec in men and >470 msec in women

             3. 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.

             4. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as
             resting 02 saturation of less than or equal to 90% breathing room air)

             5. Have undergone major surgery, other than diagnostic surgery, within 2 weeks prior
             to Cycle 1 Day 1

             6. Have active, uncontrolled bacterial, viral, or fungal infections, requiring
             systemic therapy

             7. 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)

             8, Are unwilling or unable to comply with procedures required in this protocol

             9. Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis
             C. Patients with history of chronic hepatitis that is currently not active are
             eligible.

             10. 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

             11. Are currently receiving any other investigational agent

             12. Have exhibited allergic reactions to a similar structural compound, biological
             agent, or formulation

             13. Have a medical conditional such as Crohn's disease or 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events
Time Frame:28 days
Safety Issue:
Description:MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose of TP-3654
Time Frame:23 months
Safety Issue:
Description:To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-3654, MTD data to be reviewed
Measure:Determine antitumor activity of TP-3654
Time Frame:20 months
Safety Issue:
Description:Assess for tumor burden by radiological assessment (computed tomography [CT] imaging) using RECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tolero Pharmaceuticals, Inc.

Trial Keywords

  • Tolero
  • Solid Tumor
  • Advanced Malignancy
  • First in Human
  • Phase 1
  • Cancer

Last Updated

May 20, 2019