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Study of TP-3654 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03715504
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
Tolero Pharmaceuticals, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: TP-3654 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 16, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2021

Arm Intervention/treatment
Experimental: Single Arm TP-3654
TP-3654 by oral administration
Drug: TP-3654
oral PIM inhibitor




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events [ Time Frame: 28 days ]
  2. Determine maximum tolerated dose (MTD) [ Time Frame: 20 months ]
    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 :
  1. Recommended Phase 2 Dose of TP-3654 [ Time Frame: 23 months ]
    To establish the Recommended Phase 2 Dose (RP2D) for future studies with TP-3654, MTD data to be reviewed

  2. Determine antitumor activity of TP-3654 [ Time Frame: 20 months ]
    Assess for tumor burden by radiological assessment (computed tomography [CT] imaging) using RECIST v1.1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03715504


Contacts
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Contact: Nissa Ashenbramer, BBA 210-639-2144 nashenbramer@toleropharma.com
Contact: Susan Smith, MSN 210-414-7702 su.smith@toleropharma.com

Locations
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United States, Massachusetts
Massachusetts General Hospital and Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Dejan Juric, MD    617-724-4000      
Principal Investigator: Dejan Juric, MD         
Sub-Investigator: Geoffrey Shapiro, MD, PhD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Siqing Fu, MD, PhD         
Principal Investigator: Siqing Fu, MD, PhD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Ignacio Garrido-Laguna, MD, PhD    801-585-0303      
Principal Investigator: Ignacio Garrido-Laguna, MD, PhD         
United States, Virginia
University of Virginia Not yet recruiting
Charlottesville, Virginia, United States, 22903
Contact: Patrick Dillon, MD         
Principal Investigator: Patrick Dillon, MD         
Sponsors and Collaborators
Tolero Pharmaceuticals, Inc.
Investigators
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Study Director: Margit Janat-Amsbury, MD, PhD Tolero Pharmaceuticals

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Responsible Party: Tolero Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03715504     History of Changes
Other Study ID Numbers: TP-3654-101
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tolero Pharmaceuticals, Inc.:
Tolero
Solid Tumor
Advanced Malignancy
First in Human
Phase 1
Cancer
Additional relevant MeSH terms:
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Neoplasms