Clinical Trial - NCT03429218

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

Recruiting

Sponsor: Tolero Pharmaceuticals, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03429218

Protocol Info

Short Description: Phase 1 TP-0184 in Advanced Solid Tumors
Long Description: A Phase I, First-in-Human, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0184 Administered Daily for 21 Days to Patients with Advanced Solid Tumors
MGH Status: Open
Sponsor: Tolero Pharmaceuticals, Inc.
Disease Program: Phase I

Next Steps


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Purpose

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 daily for 21 days in patients with advanced solid tumors.
Condition Title Intervention Phase
Advanced Solid Tumors TP-0184 Phase 1
Study Type Interventional
Official Title A Phase I, First-in-human, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP-0184 Administered Daily for 21 Days to Patients With Advanced Solid Tumors

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs) and treatment emergent adverse events [Time Frame: Day 1 - 28] [Designated as safety issue: ]

Determine maximum tolerated dose (MTD) [Time Frame: 20 months] [Designated as safety issue: ]


Secondary Outcome Measures

Recommended Phase 2 Dose of TP-0184 [Time Frame: 23 months] [Designated as safety issue: ]

Determine antitumor activity of TP-0184 [Time Frame: 20 months] [Designated as safety issue: ]

Estimated Enrollment: 40
Study Start Date: July 2018
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: February 2020
Arms Assigned Interventions

Experimental:Single Arm TP-0184

Daily dose of TP-0184 by oral administration
Drug:TP-0184
Oral daily dose

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

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

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

3. Have one or more tumors measurable or evaluable as outlined by modified RECIST v1

4. Have an Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance of ≤1

5. Have a life expectancy ≥3 months

6. Be ≥18 years of age

7. Have a negative pregnancy test (if female of childbearing potential)

8. Have acceptable liver function:

1. Bilirubin ≤1.5x upper limit of normal (ULN)

2. 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.

9. Have a negative pregnancy test (if female of childbearing potential)

10. Have acceptable liver function:

1. Bilirubin ≤1.5x upper limit of normal (ULN)

2. Aspartate aminotransferase (AST/SGOT), alanine amino-transferase (ALT/SGPT) and alkaline phosphatase ≤2.5x ULN. If liver metastases are present, then ≤5x ULN is allowed.

11. Have acceptable renal function:

1. Serum creatinine ≤1.5x ULN, OR

2. Calculated creatinine clearance ≥ 30 mL/min

12. Have acceptable hematologic status:

1. Granulocyte ≥1500 cells/mm3

2. Platelet count ≥100,000 (plt/mm3)

3. Hemoglobin ≥9 g/dL (Patients may not have received prior transfusions within 2 weeks of the first dose of TP-0184)

13. Have no clinically significant abnormalities on urinalysis

14. Have acceptable coagulation status:

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

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

15. 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 including for 30 days after the last dose of study drug (see Section 4.6.3). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

16. Have read and signed the 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. Cardiac disease, myocardial infarction within the past 6 months prior to Cycle 1 Day 1, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1 Day 1 (Appendix C)

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

3. Have a seizure disorders requiring anticonvulsant therapy

4. 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

5. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of ≤88% breathing room air)

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

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

8. Are pregnant or nursing

9. 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)

10. Are unwilling or unable to comply with procedures required in this protocol

11. 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.

12. 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

13. Are currently receiving any other investigational agent

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

15. 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03429218

Locations

  • United States, Arizona
    • Honor Health Scottsdale, Arizona, United States, 85258
  • United States, Kansas
    • University of Kansas Medical Center Research Institute Kansas City, Kansas, United States, 66160
  • United States, Massachusetts
    • Massachusetts General Hospital MGH Boston, Massachusetts, United States, 02215
  • United States, Texas
    • University of Texas Southwestern UTSW Dallas, Texas, United States, 75390-9179

Sponsors and Collaborators

Tolero Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03429218
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Tolero Pharmaceuticals, Inc.:

Tolero

Phase 1

First in human

Solid Tumors

Advanced Malignancy

Cancer

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019